DOPAMINE DOWN-REGULATION OF PROTEIN L-ISOASPARTYL METHYLTRANSFERASE IS DEPENDENT ON REACTIVE OXYGEN SPECIES IN SH-SY5Y CELLS
Identifieur interne : 000C08 ( Main/Exploration ); précédent : 000C07; suivant : 000C09DOPAMINE DOWN-REGULATION OF PROTEIN L-ISOASPARTYL METHYLTRANSFERASE IS DEPENDENT ON REACTIVE OXYGEN SPECIES IN SH-SY5Y CELLS
Auteurs : D. Ouazia [Canada] ; L.-C. Jr Levros [Canada] ; E. Rassart [Canada] ; R. R. Desrosiers [Canada]Source :
- Neuroscience [ 0306-4522 ] ; 2014.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Parkinson's disease (PD) is a chronic and progressive neurological disorder that is characterized by the loss of dopaminergic neurons in the substantia nigra. Dopamine, via the oxidative stress that it generates in the cytosol, could contribute to the selective loss of neurons observed in PD. Protein L-isoaspartyl methyltransferase (PIMT) is an enzyme that repairs L-isoaspartyl-containing proteins and possesses anti-apoptotic properties. PIMT expression has been shown to decrease with age. Together, these observations prompted us to investigate whether dopamine can regulate PIMT expression in SH-SY5Y neuroblastoma cells. Here, we report that dopamine down-regulated PIMT at both gene and protein levels. The same inhibition of PIMT protein level was caused by the electron transport chain inhibitor, rotenone, which was accompanied, in both cases, by an increase in cell death and reactive oxygen species (ROS) production. In fact, pre-treatment with the antioxidant N-acetyl cysteine blocked PIMT dopamine-associated down-regulation. PCMT1 promoter mapping experiments allowed the identification of two regions that showed different sensitivity to DA action. A first region localized between 61 and 94 bp upstream of transcription start site was very sensitive to dopamine inhibition while a second region between 41 and 61 bp appeared more resistant to dopamine inhibitory effect. The inhibition of PCMT1 promoter activity was mediated by dopamine-induced ROS since it was prevented by the hydroxyl radical scavenger N,N'-dimethylthiourea. Conversely, H2O2 inhibited in a dose-dependent manner the transcriptional activity of PCMT1 promoter. Therefore, our findings identified new molecular mechanisms, cytosolic dopamine and its resulting ROS, as inhibitors of PIMT expression. This suggests that ROS generated from cytosolic dopamine could reduce both the PCMT1 gene promoter activity and the PIMT protein level thus decreasing its capacity to repair proteins involved in apoptosis and could contribute to neuronal cell death observed in PD.
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 000022
- to stream PascalFrancis, to step Curation: 000B96
- to stream PascalFrancis, to step Checkpoint: 000028
- to stream Main, to step Merge: 000C13
- to stream Main, to step Curation: 000C08
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">DOPAMINE DOWN-REGULATION OF PROTEIN L-ISOASPARTYL METHYLTRANSFERASE IS DEPENDENT ON REACTIVE OXYGEN SPECIES IN SH-SY5Y CELLS</title>
<author><name sortKey="Ouazia, D" sort="Ouazia, D" uniqKey="Ouazia D" first="D." last="Ouazia">D. Ouazia</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Université du Québec à Montréal, Département de chimie, C.P. 8888, Succursale Centre-Ville</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montréal, Québec H3C 3P8</wicri:noRegion>
<orgName type="university">Université du Québec à Montréal</orgName>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Levros, L C Jr" sort="Levros, L C Jr" uniqKey="Levros L" first="L.-C. Jr" last="Levros">L.-C. Jr Levros</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université du Québec à Montréal</orgName>
</affiliation>
</author>
<author><name sortKey="Rassart, E" sort="Rassart, E" uniqKey="Rassart E" first="E." last="Rassart">E. Rassart</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université du Québec à Montréal</orgName>
</affiliation>
</author>
<author><name sortKey="Desrosiers, R R" sort="Desrosiers, R R" uniqKey="Desrosiers R" first="R. R." last="Desrosiers">R. R. Desrosiers</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Université du Québec à Montréal, Département de chimie, C.P. 8888, Succursale Centre-Ville</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montréal, Québec H3C 3P8</wicri:noRegion>
<orgName type="university">Université du Québec à Montréal</orgName>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">14-0151176</idno>
<date when="2014">2014</date>
<idno type="stanalyst">PASCAL 14-0151176 INIST</idno>
<idno type="RBID">Pascal:14-0151176</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000022</idno>
<idno type="wicri:Area/PascalFrancis/Curation">000B96</idno>
<idno type="wicri:Area/PascalFrancis/Checkpoint">000028</idno>
<idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000028</idno>
<idno type="wicri:doubleKey">0306-4522:2014:Ouazia D:dopamine:down:regulation</idno>
<idno type="wicri:Area/Main/Merge">000C13</idno>
<idno type="wicri:Area/Main/Curation">000C08</idno>
<idno type="wicri:Area/Main/Exploration">000C08</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">DOPAMINE DOWN-REGULATION OF PROTEIN L-ISOASPARTYL METHYLTRANSFERASE IS DEPENDENT ON REACTIVE OXYGEN SPECIES IN SH-SY5Y CELLS</title>
<author><name sortKey="Ouazia, D" sort="Ouazia, D" uniqKey="Ouazia D" first="D." last="Ouazia">D. Ouazia</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Université du Québec à Montréal, Département de chimie, C.P. 8888, Succursale Centre-Ville</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montréal, Québec H3C 3P8</wicri:noRegion>
<orgName type="university">Université du Québec à Montréal</orgName>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Levros, L C Jr" sort="Levros, L C Jr" uniqKey="Levros L" first="L.-C. Jr" last="Levros">L.-C. Jr Levros</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université du Québec à Montréal</orgName>
</affiliation>
</author>
<author><name sortKey="Rassart, E" sort="Rassart, E" uniqKey="Rassart E" first="E." last="Rassart">E. Rassart</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université du Québec à Montréal</orgName>
</affiliation>
</author>
<author><name sortKey="Desrosiers, R R" sort="Desrosiers, R R" uniqKey="Desrosiers R" first="R. R." last="Desrosiers">R. R. Desrosiers</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Université du Québec à Montréal, Département de chimie, C.P. 8888, Succursale Centre-Ville</s1>
<s2>Montréal, Québec H3C 3P8</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Montréal, Québec H3C 3P8</wicri:noRegion>
<orgName type="university">Université du Québec à Montréal</orgName>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Neuroscience</title>
<title level="j" type="abbreviated">Neuroscience</title>
<idno type="ISSN">0306-4522</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Neuroscience</title>
<title level="j" type="abbreviated">Neuroscience</title>
<idno type="ISSN">0306-4522</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine</term>
<term>Methyltransferases</term>
<term>Oxidative stress</term>
<term>Parkinson disease</term>
<term>Protein</term>
<term>Reactive oxygen species</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Dopamine</term>
<term>Protéine</term>
<term>Methyltransferases</term>
<term>Espèces réactives de l'oxygène</term>
<term>Stress oxydatif</term>
<term>Maladie de Parkinson</term>
<term>Lignée SHSY5Y</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a chronic and progressive neurological disorder that is characterized by the loss of dopaminergic neurons in the substantia nigra. Dopamine, via the oxidative stress that it generates in the cytosol, could contribute to the selective loss of neurons observed in PD. Protein L-isoaspartyl methyltransferase (PIMT) is an enzyme that repairs L-isoaspartyl-containing proteins and possesses anti-apoptotic properties. PIMT expression has been shown to decrease with age. Together, these observations prompted us to investigate whether dopamine can regulate PIMT expression in SH-SY5Y neuroblastoma cells. Here, we report that dopamine down-regulated PIMT at both gene and protein levels. The same inhibition of PIMT protein level was caused by the electron transport chain inhibitor, rotenone, which was accompanied, in both cases, by an increase in cell death and reactive oxygen species (ROS) production. In fact, pre-treatment with the antioxidant N-acetyl cysteine blocked PIMT dopamine-associated down-regulation. PCMT1 promoter mapping experiments allowed the identification of two regions that showed different sensitivity to DA action. A first region localized between 61 and 94 bp upstream of transcription start site was very sensitive to dopamine inhibition while a second region between 41 and 61 bp appeared more resistant to dopamine inhibitory effect. The inhibition of PCMT1 promoter activity was mediated by dopamine-induced ROS since it was prevented by the hydroxyl radical scavenger N,N'-dimethylthiourea. Conversely, H<sub>2</sub>
O<sub>2</sub>
inhibited in a dose-dependent manner the transcriptional activity of PCMT1 promoter. Therefore, our findings identified new molecular mechanisms, cytosolic dopamine and its resulting ROS, as inhibitors of PIMT expression. This suggests that ROS generated from cytosolic dopamine could reduce both the PCMT1 gene promoter activity and the PIMT protein level thus decreasing its capacity to repair proteins involved in apoptosis and could contribute to neuronal cell death observed in PD.</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
</country>
<region><li>Québec</li>
</region>
<settlement><li>Montréal</li>
</settlement>
<orgName><li>Université du Québec à Montréal</li>
</orgName>
</list>
<tree><country name="Canada"><region name="Québec"><name sortKey="Ouazia, D" sort="Ouazia, D" uniqKey="Ouazia D" first="D." last="Ouazia">D. Ouazia</name>
</region>
<name sortKey="Desrosiers, R R" sort="Desrosiers, R R" uniqKey="Desrosiers R" first="R. R." last="Desrosiers">R. R. Desrosiers</name>
<name sortKey="Levros, L C Jr" sort="Levros, L C Jr" uniqKey="Levros L" first="L.-C. Jr" last="Levros">L.-C. Jr Levros</name>
<name sortKey="Rassart, E" sort="Rassart, E" uniqKey="Rassart E" first="E." last="Rassart">E. Rassart</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C08 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000C08 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Canada |area= ParkinsonCanadaV1 |flux= Main |étape= Exploration |type= RBID |clé= Pascal:14-0151176 |texte= DOPAMINE DOWN-REGULATION OF PROTEIN L-ISOASPARTYL METHYLTRANSFERASE IS DEPENDENT ON REACTIVE OXYGEN SPECIES IN SH-SY5Y CELLS }}
This area was generated with Dilib version V0.6.29. |