Critical cysteines in Akt1 regulate its activity and proteasomal degradation: implications for neurodegenerative diseases.
Identifieur interne : 000670 ( Main/Exploration ); précédent : 000669; suivant : 000671Critical cysteines in Akt1 regulate its activity and proteasomal degradation: implications for neurodegenerative diseases.
Auteurs : Faraz Ahmad [Inde] ; Prakash Nidadavolu [Inde] ; Lalitha Durgadoss [Inde] ; Vijayalakshmi Ravindranath [Inde]Source :
- Free radical biology & medicine [ 1873-4596 ] ; 2014.
Descripteurs français
- KwdFr :
- Acétylcystéine (pharmacologie), Animaux (MeSH), Calmoduline (pharmacologie), Cystéine (composition chimique), Cystéine (génétique), Cystéine (métabolisme), Glutarédoxines (antagonistes et inhibiteurs), Humains (MeSH), Lignée cellulaire tumorale (MeSH), Maladie de Parkinson (métabolisme), Mutagenèse dirigée (MeSH), Mutation (génétique), Phosphorylation (effets des médicaments et des substances chimiques), Proteasome endopeptidase complex (métabolisme), Protein Phosphatase 2 (métabolisme), Protein-disulfide reductase (glutathione) (antagonistes et inhibiteurs), Protéines proto-oncogènes c-akt (composition chimique), Protéines proto-oncogènes c-akt (génétique), Protéines proto-oncogènes c-akt (métabolisme), Protéolyse (MeSH), Régulation négative (génétique), Souris (MeSH), Survie cellulaire (effets des médicaments et des substances chimiques), Transduction du signal (génétique).
- MESH :
- antagonistes et inhibiteurs : Glutarédoxines, Protein-disulfide reductase (glutathione).
- composition chimique : Cystéine, Protéines proto-oncogènes c-akt.
- effets des médicaments et des substances chimiques : Phosphorylation, Survie cellulaire.
- génétique : Cystéine, Mutation, Protéines proto-oncogènes c-akt, Régulation négative, Transduction du signal.
- métabolisme : Cystéine, Maladie de Parkinson, Proteasome endopeptidase complex, Protein Phosphatase 2, Protéines proto-oncogènes c-akt.
- pharmacologie : Acétylcystéine, Calmoduline.
- Animaux, Humains, Lignée cellulaire tumorale, Mutagenèse dirigée, Protéolyse, Souris.
English descriptors
- KwdEn :
- Acetylcysteine (pharmacology), Animals (MeSH), Calmodulin (pharmacology), Cell Line, Tumor (MeSH), Cell Survival (drug effects), Cysteine (chemistry), Cysteine (genetics), Cysteine (metabolism), Down-Regulation (genetics), Glutaredoxins (antagonists & inhibitors), Humans (MeSH), Mice (MeSH), Mutagenesis, Site-Directed (MeSH), Mutation (genetics), Parkinson Disease (metabolism), Phosphorylation (drug effects), Proteasome Endopeptidase Complex (metabolism), Protein Disulfide Reductase (Glutathione) (antagonists & inhibitors), Protein Phosphatase 2 (metabolism), Proteolysis (MeSH), Proto-Oncogene Proteins c-akt (chemistry), Proto-Oncogene Proteins c-akt (genetics), Proto-Oncogene Proteins c-akt (metabolism), Signal Transduction (genetics).
- MESH :
- chemical , antagonists & inhibitors : Glutaredoxins, Protein Disulfide Reductase (Glutathione).
- chemical , chemistry : Cysteine, Proto-Oncogene Proteins c-akt.
- chemical , genetics : Cysteine, Proto-Oncogene Proteins c-akt.
- chemical , metabolism : Cysteine, Proteasome Endopeptidase Complex, Protein Phosphatase 2, Proto-Oncogene Proteins c-akt.
- chemical , pharmacology : Acetylcysteine, Calmodulin.
- drug effects : Cell Survival, Phosphorylation.
- genetics : Down-Regulation, Mutation, Signal Transduction.
- metabolism : Parkinson Disease.
- Animals, Cell Line, Tumor, Humans, Mice, Mutagenesis, Site-Directed, Proteolysis.
Abstract
Impaired Akt1 signaling is observed in neurodegenerative diseases, including Parkinson׳s disease (PD). In PD models oxidative modification of Akt1 leads to its dephosphorylation and consequent loss of its kinase activity. To explore the underlying mechanism we exposed Neuro2A cells to cadmium, a pan inhibitor of protein thiol disulfide oxidoreductases, including glutaredoxin 1 (Grx1), or downregulated Grx1, which led to dephosphorylation of Akt1, loss of its kinase activity, and also decreased Akt1 protein levels. Mutation of cysteines to serines at 296 and 310 in Akt1 did not affect its basal kinase activity but abolished cadmium- and Grx1 downregulation-induced reduction in Akt1 kinase activity, indicating their critical role in redox modulation of Akt1 function and turnover. Cadmium-induced decrease in phosphorylated Akt1 correlated with increased association of wild-type (WT) Akt1 with PP2A, which was absent in the C296-310S Akt1 mutant and was also abolished by N-acetylcysteine treatment. Further, increased proteasomal degradation of Akt1 by cadmium was not seen in the C296-310S Akt1 mutant, indicating that oxidation of cysteine residues facilitates degradation of WT Akt1. Moreover, preventing oxidative modification of Akt1 cysteines 296 and 310 by mutating them to serines increased the cell survival effects of Akt1. Thus, in neurodegenerative states such as PD, maintaining the thiol status of cysteines 296 and 310 in Akt1 would be critical for Akt1 kinase activity and for preventing its degradation by proteasomes. Preventing downregulation of Akt signaling not only has long-range consequences for cell survival but could also affect the multiple roles that Akt plays, including in the Akt-mTOR signaling cascade.
DOI: 10.1016/j.freeradbiomed.2014.06.004
PubMed: 24933620
Affiliations:
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Electronic address: viji@cns.iisc.ernet.in.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Centre for Neuroscience, Indian Institute of Science, Bangalore 560012</wicri:regionArea><wicri:noRegion>Bangalore 560012</wicri:noRegion></affiliation></author></analytic><series><title level="j">Free radical biology & medicine</title><idno type="eISSN">1873-4596</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetylcysteine (pharmacology)</term><term>Animals (MeSH)</term><term>Calmodulin (pharmacology)</term><term>Cell Line, Tumor (MeSH)</term><term>Cell Survival (drug effects)</term><term>Cysteine (chemistry)</term><term>Cysteine (genetics)</term><term>Cysteine (metabolism)</term><term>Down-Regulation (genetics)</term><term>Glutaredoxins (antagonists & inhibitors)</term><term>Humans (MeSH)</term><term>Mice (MeSH)</term><term>Mutagenesis, Site-Directed (MeSH)</term><term>Mutation (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Phosphorylation (drug effects)</term><term>Proteasome Endopeptidase Complex (metabolism)</term><term>Protein Disulfide Reductase (Glutathione) (antagonists & inhibitors)</term><term>Protein Phosphatase 2 (metabolism)</term><term>Proteolysis (MeSH)</term><term>Proto-Oncogene Proteins c-akt (chemistry)</term><term>Proto-Oncogene Proteins c-akt (genetics)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>Signal Transduction (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acétylcystéine (pharmacologie)</term><term>Animaux (MeSH)</term><term>Calmoduline (pharmacologie)</term><term>Cystéine (composition chimique)</term><term>Cystéine (génétique)</term><term>Cystéine (métabolisme)</term><term>Glutarédoxines (antagonistes et inhibiteurs)</term><term>Humains (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Maladie de Parkinson (métabolisme)</term><term>Mutagenèse dirigée (MeSH)</term><term>Mutation (génétique)</term><term>Phosphorylation (effets des médicaments et des substances chimiques)</term><term>Proteasome endopeptidase complex (métabolisme)</term><term>Protein Phosphatase 2 (métabolisme)</term><term>Protein-disulfide reductase (glutathione) (antagonistes et inhibiteurs)</term><term>Protéines proto-oncogènes c-akt (composition chimique)</term><term>Protéines proto-oncogènes c-akt (génétique)</term><term>Protéines proto-oncogènes c-akt (métabolisme)</term><term>Protéolyse (MeSH)</term><term>Régulation négative (génétique)</term><term>Souris (MeSH)</term><term>Survie cellulaire (effets des médicaments et des substances chimiques)</term><term>Transduction du signal (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Glutaredoxins</term><term>Protein Disulfide Reductase (Glutathione)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cysteine</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine</term><term>Proteasome Endopeptidase Complex</term><term>Protein Phosphatase 2</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Acetylcysteine</term><term>Calmodulin</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Glutarédoxines</term><term>Protein-disulfide reductase (glutathione)</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Cystéine</term><term>Protéines proto-oncogènes c-akt</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term><term>Phosphorylation</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Phosphorylation</term><term>Survie cellulaire</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Down-Regulation</term><term>Mutation</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cystéine</term><term>Mutation</term><term>Protéines proto-oncogènes c-akt</term><term>Régulation négative</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cystéine</term><term>Maladie de Parkinson</term><term>Proteasome endopeptidase complex</term><term>Protein Phosphatase 2</term><term>Protéines proto-oncogènes c-akt</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acétylcystéine</term><term>Calmoduline</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Humans</term><term>Mice</term><term>Mutagenesis, Site-Directed</term><term>Proteolysis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mutagenèse dirigée</term><term>Protéolyse</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Impaired Akt1 signaling is observed in neurodegenerative diseases, including Parkinson׳s disease (PD). In PD models oxidative modification of Akt1 leads to its dephosphorylation and consequent loss of its kinase activity. To explore the underlying mechanism we exposed Neuro2A cells to cadmium, a pan inhibitor of protein thiol disulfide oxidoreductases, including glutaredoxin 1 (Grx1), or downregulated Grx1, which led to dephosphorylation of Akt1, loss of its kinase activity, and also decreased Akt1 protein levels. Mutation of cysteines to serines at 296 and 310 in Akt1 did not affect its basal kinase activity but abolished cadmium- and Grx1 downregulation-induced reduction in Akt1 kinase activity, indicating their critical role in redox modulation of Akt1 function and turnover. Cadmium-induced decrease in phosphorylated Akt1 correlated with increased association of wild-type (WT) Akt1 with PP2A, which was absent in the C296-310S Akt1 mutant and was also abolished by N-acetylcysteine treatment. Further, increased proteasomal degradation of Akt1 by cadmium was not seen in the C296-310S Akt1 mutant, indicating that oxidation of cysteine residues facilitates degradation of WT Akt1. Moreover, preventing oxidative modification of Akt1 cysteines 296 and 310 by mutating them to serines increased the cell survival effects of Akt1. Thus, in neurodegenerative states such as PD, maintaining the thiol status of cysteines 296 and 310 in Akt1 would be critical for Akt1 kinase activity and for preventing its degradation by proteasomes. Preventing downregulation of Akt signaling not only has long-range consequences for cell survival but could also affect the multiple roles that Akt plays, including in the Akt-mTOR signaling cascade. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24933620</PMID><DateCompleted><Year>2015</Year><Month>06</Month><Day>01</Day></DateCompleted><DateRevised><Year>2014</Year><Month>08</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-4596</ISSN><JournalIssue CitedMedium="Internet"><Volume>74</Volume><PubDate><Year>2014</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Free radical biology & medicine</Title><ISOAbbreviation>Free Radic Biol Med</ISOAbbreviation></Journal><ArticleTitle>Critical cysteines in Akt1 regulate its activity and proteasomal degradation: implications for neurodegenerative diseases.</ArticleTitle><Pagination><MedlinePgn>118-28</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.freeradbiomed.2014.06.004</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0891-5849(14)00256-1</ELocationID><Abstract><AbstractText>Impaired Akt1 signaling is observed in neurodegenerative diseases, including Parkinson׳s disease (PD). In PD models oxidative modification of Akt1 leads to its dephosphorylation and consequent loss of its kinase activity. To explore the underlying mechanism we exposed Neuro2A cells to cadmium, a pan inhibitor of protein thiol disulfide oxidoreductases, including glutaredoxin 1 (Grx1), or downregulated Grx1, which led to dephosphorylation of Akt1, loss of its kinase activity, and also decreased Akt1 protein levels. Mutation of cysteines to serines at 296 and 310 in Akt1 did not affect its basal kinase activity but abolished cadmium- and Grx1 downregulation-induced reduction in Akt1 kinase activity, indicating their critical role in redox modulation of Akt1 function and turnover. Cadmium-induced decrease in phosphorylated Akt1 correlated with increased association of wild-type (WT) Akt1 with PP2A, which was absent in the C296-310S Akt1 mutant and was also abolished by N-acetylcysteine treatment. Further, increased proteasomal degradation of Akt1 by cadmium was not seen in the C296-310S Akt1 mutant, indicating that oxidation of cysteine residues facilitates degradation of WT Akt1. Moreover, preventing oxidative modification of Akt1 cysteines 296 and 310 by mutating them to serines increased the cell survival effects of Akt1. Thus, in neurodegenerative states such as PD, maintaining the thiol status of cysteines 296 and 310 in Akt1 would be critical for Akt1 kinase activity and for preventing its degradation by proteasomes. Preventing downregulation of Akt signaling not only has long-range consequences for cell survival but could also affect the multiple roles that Akt plays, including in the Akt-mTOR signaling cascade. </AbstractText><CopyrightInformation>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ahmad</LastName><ForeName>Faraz</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nidadavolu</LastName><ForeName>Prakash</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Durgadoss</LastName><ForeName>Lalitha</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ravindranath</LastName><ForeName>Vijayalakshmi</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, India. Electronic address: viji@cns.iisc.ernet.in.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>06</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Free Radic Biol Med</MedlineTA><NlmUniqueID>8709159</NlmUniqueID><ISSNLinking>0891-5849</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002147">Calmodulin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C516006">Glrx protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.8.4.2</RegistryNumber><NameOfSubstance UI="D011490">Protein Disulfide Reductase (Glutathione)</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C514862">Akt1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.3.16</RegistryNumber><NameOfSubstance UI="D054648">Protein Phosphatase 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.25.1</RegistryNumber><NameOfSubstance UI="D046988">Proteasome Endopeptidase Complex</NameOfSubstance></Chemical><Chemical><RegistryNumber>K848JZ4886</RegistryNumber><NameOfSubstance UI="D003545">Cysteine</NameOfSubstance></Chemical><Chemical><RegistryNumber>WYQ7N0BPYC</RegistryNumber><NameOfSubstance UI="D000111">Acetylcysteine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000111" MajorTopicYN="N">Acetylcysteine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002147" MajorTopicYN="N">Calmodulin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003545" MajorTopicYN="N">Cysteine</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015536" MajorTopicYN="N">Down-Regulation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016297" MajorTopicYN="N">Mutagenesis, Site-Directed</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D046988" MajorTopicYN="N">Proteasome Endopeptidase Complex</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011490" MajorTopicYN="N">Protein Disulfide Reductase (Glutathione)</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054648" MajorTopicYN="N">Protein Phosphatase 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059748" MajorTopicYN="N">Proteolysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Free radicals</Keyword><Keyword MajorTopicYN="N">Glutaredoxin</Keyword><Keyword MajorTopicYN="N">Oxidative stress</Keyword><Keyword MajorTopicYN="N">PP2A</Keyword><Keyword MajorTopicYN="N">Parkinson disease</Keyword><Keyword MajorTopicYN="N">Protein thiols</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year><Month>12</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>06</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>06</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>6</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>6</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>6</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24933620</ArticleId><ArticleId IdType="pii">S0891-5849(14)00256-1</ArticleId><ArticleId IdType="doi">10.1016/j.freeradbiomed.2014.06.004</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Inde</li></country></list><tree><country name="Inde"><noRegion><name sortKey="Ahmad, Faraz" sort="Ahmad, Faraz" uniqKey="Ahmad F" first="Faraz" last="Ahmad">Faraz Ahmad</name></noRegion><name sortKey="Durgadoss, Lalitha" sort="Durgadoss, Lalitha" uniqKey="Durgadoss L" first="Lalitha" last="Durgadoss">Lalitha Durgadoss</name><name sortKey="Nidadavolu, Prakash" sort="Nidadavolu, Prakash" uniqKey="Nidadavolu P" first="Prakash" last="Nidadavolu">Prakash Nidadavolu</name><name sortKey="Ravindranath, Vijayalakshmi" sort="Ravindranath, Vijayalakshmi" uniqKey="Ravindranath V" first="Vijayalakshmi" last="Ravindranath">Vijayalakshmi Ravindranath</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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