Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells
Identifieur interne : 002664 ( Main/Corpus ); précédent : 002663; suivant : 002665Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells
Auteurs : Masashi Kitazawa ; Vellareddy Anantharam ; Anumantha G. KanthasamySource :
- Free Radical Biology and Medicine [ 0891-5849 ] ; 2001.
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Abstract
We examined the acute toxicity of dieldrin, a possible environmental risk factor of Parkinson’s disease, in a dopaminergic cell model, PC12 cells, to determine early cellular events underlying the pesticide-induced degenerative processes. EC50 for 1 h dieldrin exposure was 143 μM for PC12 cells, whereas EC50 for non-dopaminergic cells was 292–351 μM, indicating that dieldrin is more toxic to dopaminergic cells. Dieldrin also induced rapid, dose-dependent releases of dopamine and its metabolite, DOPAC, resulting in depletion of intracellular dopamine. Additionally, dieldrin exposure caused depolarization of mitochondrial membrane potential in a dose-dependent manner. Flow cytometric analysis showed generation of reactive oxygen species (ROS) within 5 min of dieldrin treatment, and significant increases in lipid peroxidation were also detected following 1 h exposure. ROS generation was remarkably inhibited in the presence of SOD. Dieldrin-induced apoptosis was significantly attenuated by both SOD and MnTBAP (SOD mimetic), suggesting that dieldrin-induced superoxide radicals serve as important signals in initiation of apoptosis. Furthermore, pretreatment with deprenyl (MAO-inhibitor) or α-methyl-L-p-tyrosine (TH-inhibitor) also suppressed dieldrin-induced ROS generation and DNA fragmentation. Taken together, these results suggest that rapid release of dopamine and generation of ROS are early cellular events that may account for dieldrin-induced apoptotic cell death in dopaminergic cells.
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DOI: 10.1016/S0891-5849(01)00726-2
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title><author><name sortKey="Kitazawa, Masashi" sort="Kitazawa, Masashi" uniqKey="Kitazawa M" first="Masashi" last="Kitazawa">Masashi Kitazawa</name><affiliation><mods:affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</mods:affiliation></affiliation></author><author><name sortKey="Anantharam, Vellareddy" sort="Anantharam, Vellareddy" uniqKey="Anantharam V" first="Vellareddy" last="Anantharam">Vellareddy Anantharam</name><affiliation><mods:affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</mods:affiliation></affiliation></author><author><name sortKey="Kanthasamy, Anumantha G" sort="Kanthasamy, Anumantha G" uniqKey="Kanthasamy A" first="Anumantha G." last="Kanthasamy">Anumantha G. Kanthasamy</name><affiliation><mods:affiliation>E-mail: akanthas@iastate.edu</mods:affiliation></affiliation><affiliation><mods:affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1A2C753DE5879713EDFB59D5A0044DB65557B256</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1016/S0891-5849(01)00726-2</idno><idno type="url">https://api.istex.fr/document/1A2C753DE5879713EDFB59D5A0044DB65557B256/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002664</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title><author><name sortKey="Kitazawa, Masashi" sort="Kitazawa, Masashi" uniqKey="Kitazawa M" first="Masashi" last="Kitazawa">Masashi Kitazawa</name><affiliation><mods:affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</mods:affiliation></affiliation></author><author><name sortKey="Anantharam, Vellareddy" sort="Anantharam, Vellareddy" uniqKey="Anantharam V" first="Vellareddy" last="Anantharam">Vellareddy Anantharam</name><affiliation><mods:affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</mods:affiliation></affiliation></author><author><name sortKey="Kanthasamy, Anumantha G" sort="Kanthasamy, Anumantha G" uniqKey="Kanthasamy A" first="Anumantha G." last="Kanthasamy">Anumantha G. Kanthasamy</name><affiliation><mods:affiliation>E-mail: akanthas@iastate.edu</mods:affiliation></affiliation><affiliation><mods:affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Free Radical Biology and Medicine</title><title level="j" type="abbrev">FRB</title><idno type="ISSN">0891-5849</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">31</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1473">1473</biblScope><biblScope unit="page" to="1485">1485</biblScope></imprint><idno type="ISSN">0891-5849</idno></series><idno type="istex">1A2C753DE5879713EDFB59D5A0044DB65557B256</idno><idno type="DOI">10.1016/S0891-5849(01)00726-2</idno><idno type="PII">S0891-5849(01)00726-2</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0891-5849</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>5-HIAA</term><term>ABTS</term><term>Apoptosis</term><term>DOPAC</term><term>Dieldrin</term><term>Dopamine</term><term>EDTA</term><term>Free radicals</term><term>GSH</term><term>HPLC-EC</term><term>HVA</term><term>L-DOPA</term><term>LDH</term><term>MAO</term><term>MMT</term><term>MPTP</term><term>MTT</term><term>MnTBAP</term><term>NADH</term><term>Oxidative stress</term><term>PC12 Cells</term><term>Parkinson’s disease</term><term>ROS</term><term>SNc</term><term>SOD</term><term>Superoxide</term><term>TH</term><term>α-MPT</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We examined the acute toxicity of dieldrin, a possible environmental risk factor of Parkinson’s disease, in a dopaminergic cell model, PC12 cells, to determine early cellular events underlying the pesticide-induced degenerative processes. EC50 for 1 h dieldrin exposure was 143 μM for PC12 cells, whereas EC50 for non-dopaminergic cells was 292–351 μM, indicating that dieldrin is more toxic to dopaminergic cells. Dieldrin also induced rapid, dose-dependent releases of dopamine and its metabolite, DOPAC, resulting in depletion of intracellular dopamine. Additionally, dieldrin exposure caused depolarization of mitochondrial membrane potential in a dose-dependent manner. Flow cytometric analysis showed generation of reactive oxygen species (ROS) within 5 min of dieldrin treatment, and significant increases in lipid peroxidation were also detected following 1 h exposure. ROS generation was remarkably inhibited in the presence of SOD. Dieldrin-induced apoptosis was significantly attenuated by both SOD and MnTBAP (SOD mimetic), suggesting that dieldrin-induced superoxide radicals serve as important signals in initiation of apoptosis. Furthermore, pretreatment with deprenyl (MAO-inhibitor) or α-methyl-L-p-tyrosine (TH-inhibitor) also suppressed dieldrin-induced ROS generation and DNA fragmentation. Taken together, these results suggest that rapid release of dopamine and generation of ROS are early cellular events that may account for dieldrin-induced apoptotic cell death in dopaminergic cells.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Masashi Kitazawa</name><affiliations><json:string>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</json:string></affiliations></json:item><json:item><name>Vellareddy Anantharam</name><affiliations><json:string>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</json:string></affiliations></json:item><json:item><name>Anumantha G. Kanthasamy</name><affiliations><json:string>E-mail: akanthas@iastate.edu</json:string><json:string>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Original contribution</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dieldrin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PC12 Cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Oxidative stress</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Superoxide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Apoptosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson’s disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Free radicals</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ABTS : 2,2′-azino-di-(3-ethylbenzthiazoline sulfonate (6)) diammonium salt</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>α-MPT : α-methyl-L-p-tyrosine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EDTA : ethylenediaminetetraacetic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GSH : glutathione</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>5-HIAA : 5-hydroxyindoleacetic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HPLC-EC : high-performance liquid chromatography with electrochemical detection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HVA : homovanillic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LDH : lactate dehydrogenase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DOPAC : 3,4-dihydroxyphenylacetic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>L-DOPA : L-3,4-dihydroxyphenylalanine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MAO : monoamine oxidase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MMT : methylcyclopentadienyl manganese tricarbonyl</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MnTBAP : Mn(III)tetrakis(4-benzoic acid)porphyrin chloride</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MPTP : 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MTT : 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl tetrazolium bromide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NADH : α-nicotineamide adenine dinucleotide (reduced form)</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ROS : reactive oxygen species</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNc : substantia nigra pars compacta</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SOD : superoxide dismutase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TH : tyrosine hydroxylase</value></json:item></subject><language><json:string>eng</json:string></language><abstract>We examined the acute toxicity of dieldrin, a possible environmental risk factor of Parkinson’s disease, in a dopaminergic cell model, PC12 cells, to determine early cellular events underlying the pesticide-induced degenerative processes. EC50 for 1 h dieldrin exposure was 143 μM for PC12 cells, whereas EC50 for non-dopaminergic cells was 292–351 μM, indicating that dieldrin is more toxic to dopaminergic cells. Dieldrin also induced rapid, dose-dependent releases of dopamine and its metabolite, DOPAC, resulting in depletion of intracellular dopamine. Additionally, dieldrin exposure caused depolarization of mitochondrial membrane potential in a dose-dependent manner. Flow cytometric analysis showed generation of reactive oxygen species (ROS) within 5 min of dieldrin treatment, and significant increases in lipid peroxidation were also detected following 1 h exposure. ROS generation was remarkably inhibited in the presence of SOD. Dieldrin-induced apoptosis was significantly attenuated by both SOD and MnTBAP (SOD mimetic), suggesting that dieldrin-induced superoxide radicals serve as important signals in initiation of apoptosis. Furthermore, pretreatment with deprenyl (MAO-inhibitor) or α-methyl-L-p-tyrosine (TH-inhibitor) also suppressed dieldrin-induced ROS generation and DNA fragmentation. Taken together, these results suggest that rapid release of dopamine and generation of ROS are early cellular events that may account for dieldrin-induced apoptotic cell death in dopaminergic cells.</abstract><qualityIndicators><score>7.412</score><pdfVersion>1.2</pdfVersion><pdfPageSize>587 x 785 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>29</keywordCount><abstractCharCount>1509</abstractCharCount><pdfWordCount>7764</pdfWordCount><pdfCharCount>51184</pdfCharCount><pdfPageCount>13</pdfPageCount><abstractWordCount>201</abstractWordCount></qualityIndicators><title>Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title><pii><json:string>S0891-5849(01)00726-2</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>31</volume><pii><json:string>S0891-5849(00)X0116-5</json:string></pii><pages><last>1485</last><first>1473</first></pages><issn><json:string>0891-5849</json:string></issn><issue>11</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Free Radical Biology and Medicine</title><publicationDate>2001</publicationDate></host><categories><wos><json:string>ENDOCRINOLOGY & METABOLISM</json:string><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string></wos></categories><publicationDate>2001</publicationDate><copyrightDate>2001</copyrightDate><doi><json:string>10.1016/S0891-5849(01)00726-2</json:string></doi><id>1A2C753DE5879713EDFB59D5A0044DB65557B256</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/1A2C753DE5879713EDFB59D5A0044DB65557B256/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/1A2C753DE5879713EDFB59D5A0044DB65557B256/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/1A2C753DE5879713EDFB59D5A0044DB65557B256/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/1A2C753DE5879713EDFB59D5A0044DB65557B256/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>2001</date></publicationStmt><notesStmt><note type="content">Section title: Original contribution</note><note type="content">Fig. 1: Effect of dieldrin on cell viability. PC12 cells, α-TC cells, and HCN-2 cells were exposed to 0–3000 μM dieldrin for 1 h at 37°C, and the viability was determined by a trypan blue dye exclusion. Each point represents the mean ± SEM for at least two separate experiments in duplicate. The EC50 was calculated by three-parameter nonlinear regression analysis.</note><note type="content">Fig. 2: Effect of dieldrin on extracellular LDH release in PC12 cells. PC12 cells were exposed to 0–1000 μM of dieldrin for 1 h in Krebs-Ringer at 37°C. After the exposure, cell-free extracellular supernatants were collected, and LDH activity was measured by spectrophotometer. Values represent mean ± SEM for three to five separate experiments in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗p < .05; ∗∗p < .01).</note><note type="content">Fig. 3: Effect of dieldrin on extracellular and intracellular dopamine levels in PC12 cells. Panels represent (A) extracellular dopamine and (B) intracellular dopamine levels at 1 h in dieldrin-treated PC12 cells. Dopamine content was analyzed by HPLC-EC. Data represent mean ± SEM for two to three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗p < .05; ∗∗p < .01).</note><note type="content">Fig. 4: Effect of dieldrin on extracellular and intracellular DOPAC levels in PC12 cells. Panels represent (A) extracellular and (B) intracellular DOPAC levels at 1 h in dieldrin-treated PC12 cells. DOPAC content was analyzed by HPLC-EC. Data represent mean ± SEM for two to three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗p < .05; ∗∗p < .01).</note><note type="content">Fig. 5: Effect on mitochondrial activity following dieldrin treatment. PC12 cells were treated with dieldrin for 1 h. (A) MTT assay following dieldrin treatment in PC12 cells. Relative mitochondrial activity was calculated by absorbance at 570 and 630 nm. (B) Depolarization of mitochondrial membrane potential (ΔΨm) was measured by flow cytometer using 40 nM DiOC6. Relative fluorescence intensity was calculated, and depolarization of ΔΨm was expressed as percent of control. Data represent mean ± SEM for two separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and dieldrin-treated cells (∗∗p < .01).</note><note type="content">Fig. 6: Generation of ROS following exposure to dieldrin in PC12 cells. PC12 cells were treated with varying concentrations of dieldrin (30, 100, 300 μM) for 0–30 min. Hydroethidine fluorescence intensity was measured at various time points (0, 5, 15, 30 min) by flow cytometry. Data represent mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗∗p < .01).</note><note type="content">Fig. 7: Effect of superoxide dismutase (SOD) on dieldrin-induced ROS generation. Panels represent the effect of SOD pretreatment (100 units, 5 min) on (A) 30 μM and (B) 100 μM dieldrin-treated PC12 cells at time points up to 30 min. Hydroethidine fluorescence intensity was measured by flow cytometry. Data represent the mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the dieldrin-treated cells with and without SOD pretreatment (∗∗p < .01).</note><note type="content">Fig. 8: Formation of lipid peroxides following exposure to dieldrin in PC12 cells. PC12 cells were treated with varying concentrations of dieldrin (30, 100, 300, and 500 μM) for 1 h. Dodecanyl aminofluorescein fluorescence intensity was measured by flow cytometry. Data represent the mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated cells and each treatment group (∗∗p < .01).</note><note type="content">Fig. 9: Effect of superoxide dismutase (SOD) on dieldrin-induced cytotoxicity. PC12 cells were exposed to 30 or 100 μM dieldrin for 1 h, with or without SOD (100 units) pretreatment. LDH activity was measured in the incubation buffer by spectrophotometer in 96-well format. Data represent the mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest. SOD pretreatment did not show any significant decrease in LDH activity compared to groups treated with dieldrin alone.</note><note type="content">Fig. 10: Effect of superoxide dismutase (SOD) on dieldrin-induced DNA fragmentation in PC12 cells. Panels represent results of DNA fragmentation assays in PC12 cells pretreated with (A) SOD (100 units/ml, 5 min) or (B) MnTBAP (2 μM, 30 min). DNA fragmentation was quantified by antihistone-biotin directed against histones (H1, H2A, H2B, H3, and H4) and anti-DNA-POD directed against both single- and double-stranded DNA. Data represent the mean ± SEM for two separate experiments performed in triplicate. ap < .01 compared dieldrin-treated groups with vehicle treated group using ANOVA followed by Dunnett’s posttest, and bp < .05 or cp < .01 compared SOD- or MnTBAP-treated groups with dieldrin-treated groups using t-test.</note><note type="content">Fig. 11: Hoechst 33342 staining of dieldrin-induced apoptosis in PC12 cells. Cultured PC12 cells were treated with dieldrin (100 or 300 μM) alone or in the presence of SOD (100 units) for 1 h. Hoechst 33342 was used to visualize apoptosis by a fluorescent microscope under UV illumination. Arrows indicate apoptotic features of chromatin condensation. Each image represents two separate experiments.</note><note type="content">Fig. 12: Effect of MAO-B or TH inhibitors on dieldrin-induced ROS generation and apoptosis. (A) PC12 cells were pretreated with 500 μM α-methyl-L-p-tyrosine (α-MPT) for 24 h or 100 μM deprenyl for 30 min prior to dieldrin exposure. Intracellular ROS was measured using hydroethidine in a flow cytometer during 0–15 min dieldrin exposure. The data represent the mean ± SEM from two separate experiments in triplicate. ∗p < .05 or ∗∗p < .01 compared with the dieldrin-treated group. (B) PC12 cells were pretreated with 500 μM α-MPT for 24 h or 100 μM deprenyl for 30 min prior to 100 μM dieldrin exposure for 1 h. DNA fragmentation was quantified as described in Material and Methods. Data represent the mean ± SEM for two separate experiment performed in triplicate. ∗∗p < .01 compared with dieldrin-treated group.</note><note type="content">Table 1: Levels of Dopamine and DOPAC Following TH or MAO-B Inhibitors</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title><author><persName><forename type="first">Masashi</forename><surname>Kitazawa</surname></persName><affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</affiliation></author><author><persName><forename type="first">Vellareddy</forename><surname>Anantharam</surname></persName><affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</affiliation></author><author><persName><forename type="first">Anumantha G.</forename><surname>Kanthasamy</surname></persName><email>akanthas@iastate.edu</email><affiliation>Address correspondence to: Anumantha G. Kanthasamy, Ph.D., Associate Professor, Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, 2062 Veterinary Medicine Building, Ames, IA, 50011-1250 USA; Tel: (515) 294-2516; Fax: (515) 294-2315</affiliation><affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</affiliation></author></analytic><monogr><title level="j">Free Radical Biology and Medicine</title><title level="j" type="abbrev">FRB</title><idno type="pISSN">0891-5849</idno><idno type="PII">S0891-5849(00)X0116-5</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001"></date><biblScope unit="volume">31</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1473">1473</biblScope><biblScope unit="page" to="1485">1485</biblScope></imprint></monogr><idno type="istex">1A2C753DE5879713EDFB59D5A0044DB65557B256</idno><idno type="DOI">10.1016/S0891-5849(01)00726-2</idno><idno type="PII">S0891-5849(01)00726-2</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>We examined the acute toxicity of dieldrin, a possible environmental risk factor of Parkinson’s disease, in a dopaminergic cell model, PC12 cells, to determine early cellular events underlying the pesticide-induced degenerative processes. EC50 for 1 h dieldrin exposure was 143 μM for PC12 cells, whereas EC50 for non-dopaminergic cells was 292–351 μM, indicating that dieldrin is more toxic to dopaminergic cells. Dieldrin also induced rapid, dose-dependent releases of dopamine and its metabolite, DOPAC, resulting in depletion of intracellular dopamine. Additionally, dieldrin exposure caused depolarization of mitochondrial membrane potential in a dose-dependent manner. Flow cytometric analysis showed generation of reactive oxygen species (ROS) within 5 min of dieldrin treatment, and significant increases in lipid peroxidation were also detected following 1 h exposure. ROS generation was remarkably inhibited in the presence of SOD. Dieldrin-induced apoptosis was significantly attenuated by both SOD and MnTBAP (SOD mimetic), suggesting that dieldrin-induced superoxide radicals serve as important signals in initiation of apoptosis. Furthermore, pretreatment with deprenyl (MAO-inhibitor) or α-methyl-L-p-tyrosine (TH-inhibitor) also suppressed dieldrin-induced ROS generation and DNA fragmentation. Taken together, these results suggest that rapid release of dopamine and generation of ROS are early cellular events that may account for dieldrin-induced apoptotic cell death in dopaminergic cells.</p></abstract><textClass><keywords scheme="keyword"><list><head>Article category</head><item><term>Original contribution</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Dieldrin</term></item><item><term>PC12 Cells</term></item><item><term>Oxidative stress</term></item><item><term>Dopamine</term></item><item><term>Superoxide</term></item><item><term>Apoptosis</term></item><item><term>Parkinson’s disease</term></item><item><term>Free radicals</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>ABTS</term><term>2,2′-azino-di-(3-ethylbenzthiazoline sulfonate (6)) diammonium salt</term></item><item><term>α-MPT</term><term>α-methyl-L-p-tyrosine</term></item><item><term>EDTA</term><term>ethylenediaminetetraacetic acid</term></item><item><term>GSH</term><term>glutathione</term></item><item><term>5-HIAA</term><term>5-hydroxyindoleacetic acid</term></item><item><term>HPLC-EC</term><term>high-performance liquid chromatography with electrochemical detection</term></item><item><term>HVA</term><term>homovanillic acid</term></item><item><term>LDH</term><term>lactate dehydrogenase</term></item><item><term>DOPAC</term><term>3,4-dihydroxyphenylacetic acid</term></item><item><term>L-DOPA</term><term>L-3,4-dihydroxyphenylalanine</term></item><item><term>MAO</term><term>monoamine oxidase</term></item><item><term>MMT</term><term>methylcyclopentadienyl manganese tricarbonyl</term></item><item><term>MnTBAP</term><term>Mn(III)tetrakis(4-benzoic acid)porphyrin chloride</term></item><item><term>MPTP</term><term>1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></item><item><term>MTT</term><term>3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl tetrazolium bromide</term></item><item><term>NADH</term><term>α-nicotineamide adenine dinucleotide (reduced form)</term></item><item><term>ROS</term><term>reactive oxygen species</term></item><item><term>SNc</term><term>substantia nigra pars compacta</term></item><item><term>SOD</term><term>superoxide dismutase</term></item><item><term>TH</term><term>tyrosine hydroxylase</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2001-09-06">Registration</change><change when="2001">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="GR1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="GR2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="GR3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="GR4"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="GR5"></istex:entity><istex:entity SYSTEM="gr6" NDATA="IMAGE" name="GR6"></istex:entity><istex:entity SYSTEM="gr7" NDATA="IMAGE" name="GR7"></istex:entity><istex:entity SYSTEM="gr8" NDATA="IMAGE" name="GR8"></istex:entity><istex:entity SYSTEM="gr9" NDATA="IMAGE" name="GR9"></istex:entity><istex:entity SYSTEM="gr10" NDATA="IMAGE" name="GR10"></istex:entity><istex:entity SYSTEM="gr11" NDATA="IMAGE" name="GR11"></istex:entity><istex:entity SYSTEM="gr12" NDATA="IMAGE" name="GR12"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>FRB</jid><aid>6623</aid><ce:pii>S0891-5849(01)00726-2</ce:pii><ce:doi>10.1016/S0891-5849(01)00726-2</ce:doi><ce:copyright type="full-transfer" year="2001">Elsevier Science Inc.</ce:copyright><ce:doctopics><ce:doctopic><ce:text>Original contribution</ce:text></ce:doctopic></ce:doctopics></item-info><head><ce:dochead><ce:textfn>Original contribution</ce:textfn></ce:dochead><ce:title>Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</ce:title><ce:author-group><ce:author><ce:given-name>Masashi</ce:given-name><ce:surname>Kitazawa</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Vellareddy</ce:given-name><ce:surname>Anantharam</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Anumantha G.</ce:given-name><ce:surname>Kanthasamy</ce:surname><ce:cross-ref refid="COR1">*</ce:cross-ref><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:e-address type="email">akanthas@iastate.edu</ce:e-address></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>*</ce:label><ce:text>Address correspondence to: Anumantha G. Kanthasamy, Ph.D., Associate Professor, Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, 2062 Veterinary Medicine Building, Ames, IA, 50011-1250 USA; Tel: (515) 294-2516; Fax: (515) 294-2315</ce:text></ce:correspondence></ce:author-group><ce:date-received day="12" month="4" year="2001"></ce:date-received><ce:date-accepted day="6" month="9" year="2001"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>We examined the acute toxicity of dieldrin, a possible environmental risk factor of Parkinson’s disease, in a dopaminergic cell model, PC12 cells, to determine early cellular events underlying the pesticide-induced degenerative processes. EC<ce:inf>50</ce:inf> for 1 h dieldrin exposure was 143 μM for PC12 cells, whereas EC<ce:inf>50</ce:inf> for non-dopaminergic cells was 292–351 μM, indicating that dieldrin is more toxic to dopaminergic cells. Dieldrin also induced rapid, dose-dependent releases of dopamine and its metabolite, DOPAC, resulting in depletion of intracellular dopamine. Additionally, dieldrin exposure caused depolarization of mitochondrial membrane potential in a dose-dependent manner. Flow cytometric analysis showed generation of reactive oxygen species (ROS) within 5 min of dieldrin treatment, and significant increases in lipid peroxidation were also detected following 1 h exposure. ROS generation was remarkably inhibited in the presence of SOD. Dieldrin-induced apoptosis was significantly attenuated by both SOD and MnTBAP (SOD mimetic), suggesting that dieldrin-induced superoxide radicals serve as important signals in initiation of apoptosis. Furthermore, pretreatment with deprenyl (MAO-inhibitor) or α-methyl-L-p-tyrosine (TH-inhibitor) also suppressed dieldrin-induced ROS generation and DNA fragmentation. Taken together, these results suggest that rapid release of dopamine and generation of ROS are early cellular events that may account for dieldrin-induced apoptotic cell death in dopaminergic cells.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Dieldrin</ce:text></ce:keyword><ce:keyword><ce:text>PC12 Cells</ce:text></ce:keyword><ce:keyword><ce:text>Oxidative stress</ce:text></ce:keyword><ce:keyword><ce:text>Dopamine</ce:text></ce:keyword><ce:keyword><ce:text>Superoxide</ce:text></ce:keyword><ce:keyword><ce:text>Apoptosis</ce:text></ce:keyword><ce:keyword><ce:text>Parkinson’s disease</ce:text></ce:keyword><ce:keyword><ce:text>Free radicals</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>ABTS</ce:text><ce:keyword><ce:text>2,2′-azino-di-(3-ethylbenzthiazoline sulfonate (6)) diammonium salt</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>α-MPT</ce:text><ce:keyword><ce:text>α-methyl-L-p-tyrosine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>EDTA</ce:text><ce:keyword><ce:text>ethylenediaminetetraacetic acid</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>GSH</ce:text><ce:keyword><ce:text>glutathione</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>5-HIAA</ce:text><ce:keyword><ce:text>5-hydroxyindoleacetic acid</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HPLC-EC</ce:text><ce:keyword><ce:text>high-performance liquid chromatography with electrochemical detection</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HVA</ce:text><ce:keyword><ce:text>homovanillic acid</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>LDH</ce:text><ce:keyword><ce:text>lactate dehydrogenase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>DOPAC</ce:text><ce:keyword><ce:text>3,4-dihydroxyphenylacetic acid</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>L-DOPA</ce:text><ce:keyword><ce:text>L-3,4-dihydroxyphenylalanine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MAO</ce:text><ce:keyword><ce:text>monoamine oxidase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MMT</ce:text><ce:keyword><ce:text>methylcyclopentadienyl manganese tricarbonyl</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MnTBAP</ce:text><ce:keyword><ce:text>Mn(III)tetrakis(4-benzoic acid)porphyrin chloride</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MPTP</ce:text><ce:keyword><ce:text>1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MTT</ce:text><ce:keyword><ce:text>3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl tetrazolium bromide</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>NADH</ce:text><ce:keyword><ce:text>α-nicotineamide adenine dinucleotide (reduced form)</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>ROS</ce:text><ce:keyword><ce:text>reactive oxygen species</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SNc</ce:text><ce:keyword><ce:text>substantia nigra pars compacta</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SOD</ce:text><ce:keyword><ce:text>superoxide dismutase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TH</ce:text><ce:keyword><ce:text>tyrosine hydroxylase</ce:text></ce:keyword></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells</title></titleInfo><name type="personal"><namePart type="given">Masashi</namePart><namePart type="family">Kitazawa</namePart><affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vellareddy</namePart><namePart type="family">Anantharam</namePart><affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anumantha G.</namePart><namePart type="family">Kanthasamy</namePart><affiliation>E-mail: akanthas@iastate.edu</affiliation><affiliation>Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA</affiliation><description>Address correspondence to: Anumantha G. Kanthasamy, Ph.D., Associate Professor, Parkinson Disorders Research Program, Department of Biomedical Sciences, Iowa State University, 2062 Veterinary Medicine Building, Ames, IA, 50011-1250 USA; Tel: (515) 294-2516; Fax: (515) 294-2315</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2001</dateIssued><dateValid encoding="w3cdtf">2001-09-06</dateValid><copyrightDate encoding="w3cdtf">2001</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">We examined the acute toxicity of dieldrin, a possible environmental risk factor of Parkinson’s disease, in a dopaminergic cell model, PC12 cells, to determine early cellular events underlying the pesticide-induced degenerative processes. EC50 for 1 h dieldrin exposure was 143 μM for PC12 cells, whereas EC50 for non-dopaminergic cells was 292–351 μM, indicating that dieldrin is more toxic to dopaminergic cells. Dieldrin also induced rapid, dose-dependent releases of dopamine and its metabolite, DOPAC, resulting in depletion of intracellular dopamine. Additionally, dieldrin exposure caused depolarization of mitochondrial membrane potential in a dose-dependent manner. Flow cytometric analysis showed generation of reactive oxygen species (ROS) within 5 min of dieldrin treatment, and significant increases in lipid peroxidation were also detected following 1 h exposure. ROS generation was remarkably inhibited in the presence of SOD. Dieldrin-induced apoptosis was significantly attenuated by both SOD and MnTBAP (SOD mimetic), suggesting that dieldrin-induced superoxide radicals serve as important signals in initiation of apoptosis. Furthermore, pretreatment with deprenyl (MAO-inhibitor) or α-methyl-L-p-tyrosine (TH-inhibitor) also suppressed dieldrin-induced ROS generation and DNA fragmentation. Taken together, these results suggest that rapid release of dopamine and generation of ROS are early cellular events that may account for dieldrin-induced apoptotic cell death in dopaminergic cells.</abstract><note type="content">Section title: Original contribution</note><note type="content">Fig. 1: Effect of dieldrin on cell viability. PC12 cells, α-TC cells, and HCN-2 cells were exposed to 0–3000 μM dieldrin for 1 h at 37°C, and the viability was determined by a trypan blue dye exclusion. Each point represents the mean ± SEM for at least two separate experiments in duplicate. The EC50 was calculated by three-parameter nonlinear regression analysis.</note><note type="content">Fig. 2: Effect of dieldrin on extracellular LDH release in PC12 cells. PC12 cells were exposed to 0–1000 μM of dieldrin for 1 h in Krebs-Ringer at 37°C. After the exposure, cell-free extracellular supernatants were collected, and LDH activity was measured by spectrophotometer. Values represent mean ± SEM for three to five separate experiments in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗p < .05; ∗∗p < .01).</note><note type="content">Fig. 3: Effect of dieldrin on extracellular and intracellular dopamine levels in PC12 cells. Panels represent (A) extracellular dopamine and (B) intracellular dopamine levels at 1 h in dieldrin-treated PC12 cells. Dopamine content was analyzed by HPLC-EC. Data represent mean ± SEM for two to three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗p < .05; ∗∗p < .01).</note><note type="content">Fig. 4: Effect of dieldrin on extracellular and intracellular DOPAC levels in PC12 cells. Panels represent (A) extracellular and (B) intracellular DOPAC levels at 1 h in dieldrin-treated PC12 cells. DOPAC content was analyzed by HPLC-EC. Data represent mean ± SEM for two to three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗p < .05; ∗∗p < .01).</note><note type="content">Fig. 5: Effect on mitochondrial activity following dieldrin treatment. PC12 cells were treated with dieldrin for 1 h. (A) MTT assay following dieldrin treatment in PC12 cells. Relative mitochondrial activity was calculated by absorbance at 570 and 630 nm. (B) Depolarization of mitochondrial membrane potential (ΔΨm) was measured by flow cytometer using 40 nM DiOC6. Relative fluorescence intensity was calculated, and depolarization of ΔΨm was expressed as percent of control. Data represent mean ± SEM for two separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and dieldrin-treated cells (∗∗p < .01).</note><note type="content">Fig. 6: Generation of ROS following exposure to dieldrin in PC12 cells. PC12 cells were treated with varying concentrations of dieldrin (30, 100, 300 μM) for 0–30 min. Hydroethidine fluorescence intensity was measured at various time points (0, 5, 15, 30 min) by flow cytometry. Data represent mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated group and each treatment group (∗∗p < .01).</note><note type="content">Fig. 7: Effect of superoxide dismutase (SOD) on dieldrin-induced ROS generation. Panels represent the effect of SOD pretreatment (100 units, 5 min) on (A) 30 μM and (B) 100 μM dieldrin-treated PC12 cells at time points up to 30 min. Hydroethidine fluorescence intensity was measured by flow cytometry. Data represent the mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the dieldrin-treated cells with and without SOD pretreatment (∗∗p < .01).</note><note type="content">Fig. 8: Formation of lipid peroxides following exposure to dieldrin in PC12 cells. PC12 cells were treated with varying concentrations of dieldrin (30, 100, 300, and 500 μM) for 1 h. Dodecanyl aminofluorescein fluorescence intensity was measured by flow cytometry. Data represent the mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest between the vehicle-treated cells and each treatment group (∗∗p < .01).</note><note type="content">Fig. 9: Effect of superoxide dismutase (SOD) on dieldrin-induced cytotoxicity. PC12 cells were exposed to 30 or 100 μM dieldrin for 1 h, with or without SOD (100 units) pretreatment. LDH activity was measured in the incubation buffer by spectrophotometer in 96-well format. Data represent the mean ± SEM for three separate experiments performed in triplicate. Significance was determined by ANOVA followed by Dunnett’s posttest. SOD pretreatment did not show any significant decrease in LDH activity compared to groups treated with dieldrin alone.</note><note type="content">Fig. 10: Effect of superoxide dismutase (SOD) on dieldrin-induced DNA fragmentation in PC12 cells. Panels represent results of DNA fragmentation assays in PC12 cells pretreated with (A) SOD (100 units/ml, 5 min) or (B) MnTBAP (2 μM, 30 min). DNA fragmentation was quantified by antihistone-biotin directed against histones (H1, H2A, H2B, H3, and H4) and anti-DNA-POD directed against both single- and double-stranded DNA. Data represent the mean ± SEM for two separate experiments performed in triplicate. ap < .01 compared dieldrin-treated groups with vehicle treated group using ANOVA followed by Dunnett’s posttest, and bp < .05 or cp < .01 compared SOD- or MnTBAP-treated groups with dieldrin-treated groups using t-test.</note><note type="content">Fig. 11: Hoechst 33342 staining of dieldrin-induced apoptosis in PC12 cells. Cultured PC12 cells were treated with dieldrin (100 or 300 μM) alone or in the presence of SOD (100 units) for 1 h. Hoechst 33342 was used to visualize apoptosis by a fluorescent microscope under UV illumination. Arrows indicate apoptotic features of chromatin condensation. Each image represents two separate experiments.</note><note type="content">Fig. 12: Effect of MAO-B or TH inhibitors on dieldrin-induced ROS generation and apoptosis. (A) PC12 cells were pretreated with 500 μM α-methyl-L-p-tyrosine (α-MPT) for 24 h or 100 μM deprenyl for 30 min prior to dieldrin exposure. Intracellular ROS was measured using hydroethidine in a flow cytometer during 0–15 min dieldrin exposure. The data represent the mean ± SEM from two separate experiments in triplicate. ∗p < .05 or ∗∗p < .01 compared with the dieldrin-treated group. (B) PC12 cells were pretreated with 500 μM α-MPT for 24 h or 100 μM deprenyl for 30 min prior to 100 μM dieldrin exposure for 1 h. DNA fragmentation was quantified as described in Material and Methods. Data represent the mean ± SEM for two separate experiment performed in triplicate. ∗∗p < .01 compared with dieldrin-treated group.</note><note type="content">Table 1: Levels of Dopamine and DOPAC Following TH or MAO-B Inhibitors</note><subject><genre>Article category</genre><topic>Original contribution</topic></subject><subject lang="en"><genre>Keywords</genre><topic>Dieldrin</topic><topic>PC12 Cells</topic><topic>Oxidative stress</topic><topic>Dopamine</topic><topic>Superoxide</topic><topic>Apoptosis</topic><topic>Parkinson’s disease</topic><topic>Free radicals</topic></subject><subject lang="en"><genre>Abbreviations</genre><topic>ABTS : 2,2′-azino-di-(3-ethylbenzthiazoline sulfonate (6)) diammonium salt</topic><topic>α-MPT : α-methyl-L-p-tyrosine</topic><topic>EDTA : ethylenediaminetetraacetic acid</topic><topic>GSH : glutathione</topic><topic>5-HIAA : 5-hydroxyindoleacetic acid</topic><topic>HPLC-EC : high-performance liquid chromatography with electrochemical detection</topic><topic>HVA : homovanillic acid</topic><topic>LDH : lactate dehydrogenase</topic><topic>DOPAC : 3,4-dihydroxyphenylacetic acid</topic><topic>L-DOPA : L-3,4-dihydroxyphenylalanine</topic><topic>MAO : monoamine oxidase</topic><topic>MMT : methylcyclopentadienyl manganese tricarbonyl</topic><topic>MnTBAP : Mn(III)tetrakis(4-benzoic acid)porphyrin chloride</topic><topic>MPTP : 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</topic><topic>MTT : 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl tetrazolium bromide</topic><topic>NADH : α-nicotineamide adenine dinucleotide (reduced form)</topic><topic>ROS : reactive oxygen species</topic><topic>SNc : substantia nigra pars compacta</topic><topic>SOD : superoxide dismutase</topic><topic>TH : tyrosine hydroxylase</topic></subject><relatedItem type="host"><titleInfo><title>Free Radical Biology and Medicine</title></titleInfo><titleInfo type="abbreviated"><title>FRB</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">20011201</dateIssued></originInfo><identifier type="ISSN">0891-5849</identifier><identifier type="PII">S0891-5849(00)X0116-5</identifier><part><date>20011201</date><detail type="volume"><number>31</number><caption>vol.</caption></detail><detail type="issue"><number>11</number><caption>no.</caption></detail><extent unit="issue pages"><start>1287</start><end>1522</end></extent><extent unit="pages"><start>1473</start><end>1485</end></extent></part></relatedItem><identifier type="istex">1A2C753DE5879713EDFB59D5A0044DB65557B256</identifier><identifier type="DOI">10.1016/S0891-5849(01)00726-2</identifier><identifier type="PII">S0891-5849(01)00726-2</identifier><accessCondition type="use and reproduction" contentType="">© 2001Elsevier Science Inc.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science Inc., ©2001</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/1A2C753DE5879713EDFB59D5A0044DB65557B256/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">ENDOCRINOLOGY & METABOLISM</classCode><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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