DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway
Identifieur interne : 001A70 ( Main/Exploration ); précédent : 001A69; suivant : 001A71DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway
Auteurs : Hossein Aleyasin [Canada] ; Maxime W. C. Rousseaux [Canada] ; Paul C. Marcogliese [Canada] ; Sarah J. Hewitt [Canada] ; Isabella Irrcher [Canada] ; Alvin P. Joselin [Canada] ; Mohammad Parsanejad [Canada] ; Raymond H. Kim [Canada] ; Patrizia Rizzu [Pays-Bas] ; Steve M. Callaghan [Canada] ; Ruth S. Slack [Canada] ; Tak W. Mak [Canada] ; David S. Park [Canada, Corée du Sud]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2010.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (metabolism), Analysis of Variance, Animals, Blotting, Western, Cell Fractionation, Cells, Cultured, Hydrogen Peroxide (metabolism), Immunohistochemistry, Mice, Neurons (metabolism), Neurotoxins (metabolism), Oncogene Proteins (metabolism), Oxidative Stress (physiology), Peroxiredoxins, Phosphorylation, Protein Deglycase DJ-1, Proto-Oncogene Proteins c-akt (metabolism), Signal Transduction (physiology).
- MESH :
- chemical , metabolism : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Hydrogen Peroxide, Neurotoxins, Oncogene Proteins, Proto-Oncogene Proteins c-akt.
- metabolism : Neurons.
- physiology : Oxidative Stress, Signal Transduction.
- Analysis of Variance, Animals, Blotting, Western, Cell Fractionation, Cells, Cultured, Immunohistochemistry, Mice, Peroxiredoxins, Phosphorylation, Protein Deglycase DJ-1.
Abstract
Loss-of-function DJ-1 (PARK7) mutations have been linked with a familial form of early onset Parkinson disease. Numerous studies have supported the role of DJ-1 in neuronal survival and function. Our initial studies using DJ-1-deficient neurons indicated that DJ-1 specifically protects the neurons against the damage induced by oxidative injury in multiple neuronal types and degenerative experimental paradigms, both in vitro and in vivo. However, the manner by which oxidative stress-induced death is ameliorated by DJ-1 is not completely clear. We now present data that show the involvement of DJ-1 in modulation of AKT, a major neuronal prosurvival pathway induced upon oxidative stress. We provide evidence that DJ-1 promotes AKT phosphorylation in response to oxidative stress induced by H2O2 in vitro and in vivo following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Moreover, we show that DJ-1 is necessary for normal AKT-mediated protective effects, which can be bypassed by expression of a constitutively active form of AKT. Taken together, these data suggest that DJ-1 is crucial for full activation of AKT upon oxidative injury, which serves as one explanation for the protective effects of DJ-1.
Url:
DOI: 10.1073/pnas.0914876107
PubMed: 20133695
PubMed Central: 2840364
Affiliations:
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Le document en format XML
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Park</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cogno-Mechatronics Engineering,<institution>Pusan National University</institution>, Geumjeong GU, Busan 609 735<country>South Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20133695</idno><idno type="pmc">2840364</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840364</idno><idno type="RBID">PMC:2840364</idno><idno type="doi">10.1073/pnas.0914876107</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000655</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000655</idno><idno type="wicri:Area/Pmc/Curation">000655</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000655</idno><idno type="wicri:Area/Pmc/Checkpoint">000A57</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A57</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000D75</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000D75</idno><idno type="wicri:Area/PubMed/Curation">000D75</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000D75</idno><idno type="wicri:Area/PubMed/Checkpoint">000D75</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000D75</idno><idno type="wicri:Area/Ncbi/Merge">000C13</idno><idno type="wicri:Area/Ncbi/Curation">000C13</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C13</idno><idno type="wicri:doubleKey">0027-8424:2010:Aleyasin H:dj:protects:the</idno><idno type="wicri:Area/Main/Merge">001B80</idno><idno type="wicri:Area/Main/Curation">001A70</idno><idno type="wicri:Area/Main/Exploration">001A70</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway</title><author><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rousseaux, Maxime W C" sort="Rousseaux, Maxime W C" uniqKey="Rousseaux M" first="Maxime W. C." last="Rousseaux">Maxime W. C. Rousseaux</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Marcogliese, Paul C" sort="Marcogliese, Paul C" uniqKey="Marcogliese P" first="Paul C." last="Marcogliese">Paul C. Marcogliese</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hewitt, Sarah J" sort="Hewitt, Sarah J" uniqKey="Hewitt S" first="Sarah J." last="Hewitt">Sarah J. Hewitt</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Irrcher, Isabella" sort="Irrcher, Isabella" uniqKey="Irrcher I" first="Isabella" last="Irrcher">Isabella Irrcher</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Joselin, Alvin P" sort="Joselin, Alvin P" uniqKey="Joselin A" first="Alvin P." last="Joselin">Alvin P. Joselin</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Parsanejad, Mohammad" sort="Parsanejad, Mohammad" uniqKey="Parsanejad M" first="Mohammad" last="Parsanejad">Mohammad Parsanejad</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Section Medical Genomics, Department of Clinical Genetics,<institution>Vrije Universiteit University</institution><institution>Medical Center</institution>, Van der Boechorststraat 7, 1081 BT, Amsterdam,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Callaghan, Steve M" sort="Callaghan, Steve M" uniqKey="Callaghan S" first="Steve M." last="Callaghan">Steve M. Callaghan</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cogno-Mechatronics Engineering,<institution>Pusan National University</institution>, Geumjeong GU, Busan 609 735<country>South Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (metabolism)</term><term>Analysis of Variance</term><term>Animals</term><term>Blotting, Western</term><term>Cell Fractionation</term><term>Cells, Cultured</term><term>Hydrogen Peroxide (metabolism)</term><term>Immunohistochemistry</term><term>Mice</term><term>Neurons (metabolism)</term><term>Neurotoxins (metabolism)</term><term>Oncogene Proteins (metabolism)</term><term>Oxidative Stress (physiology)</term><term>Peroxiredoxins</term><term>Phosphorylation</term><term>Protein Deglycase DJ-1</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>Signal Transduction (physiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Hydrogen Peroxide</term><term>Neurotoxins</term><term>Oncogene Proteins</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Oxidative Stress</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Analysis of Variance</term><term>Animals</term><term>Blotting, Western</term><term>Cell Fractionation</term><term>Cells, Cultured</term><term>Immunohistochemistry</term><term>Mice</term><term>Peroxiredoxins</term><term>Phosphorylation</term><term>Protein Deglycase DJ-1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Loss-of-function DJ-1 (PARK7) mutations have been linked with a familial form of early onset Parkinson disease. Numerous studies have supported the role of DJ-1 in neuronal survival and function. Our initial studies using DJ-1-deficient neurons indicated that DJ-1 specifically protects the neurons against the damage induced by oxidative injury in multiple neuronal types and degenerative experimental paradigms, both in vitro and in vivo. However, the manner by which oxidative stress-induced death is ameliorated by DJ-1 is not completely clear. We now present data that show the involvement of DJ-1 in modulation of AKT, a major neuronal prosurvival pathway induced upon oxidative stress. We provide evidence that DJ-1 promotes AKT phosphorylation in response to oxidative stress induced by H<sub>2</sub>O<sub>2</sub> in vitro and in vivo following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Moreover, we show that DJ-1 is necessary for normal AKT-mediated protective effects, which can be bypassed by expression of a constitutively active form of AKT. Taken together, these data suggest that DJ-1 is crucial for full activation of AKT upon oxidative injury, which serves as one explanation for the protective effects of DJ-1.</p></div></front></TEI><affiliations><list><country><li>Canada</li><li>Corée du Sud</li><li>Pays-Bas</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name></noRegion><name sortKey="Callaghan, Steve M" sort="Callaghan, Steve M" uniqKey="Callaghan S" first="Steve M." last="Callaghan">Steve M. Callaghan</name><name sortKey="Hewitt, Sarah J" sort="Hewitt, Sarah J" uniqKey="Hewitt S" first="Sarah J." last="Hewitt">Sarah J. Hewitt</name><name sortKey="Irrcher, Isabella" sort="Irrcher, Isabella" uniqKey="Irrcher I" first="Isabella" last="Irrcher">Isabella Irrcher</name><name sortKey="Joselin, Alvin P" sort="Joselin, Alvin P" uniqKey="Joselin A" first="Alvin P." last="Joselin">Alvin P. Joselin</name><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><name sortKey="Marcogliese, Paul C" sort="Marcogliese, Paul C" uniqKey="Marcogliese P" first="Paul C." last="Marcogliese">Paul C. Marcogliese</name><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><name sortKey="Parsanejad, Mohammad" sort="Parsanejad, Mohammad" uniqKey="Parsanejad M" first="Mohammad" last="Parsanejad">Mohammad Parsanejad</name><name sortKey="Rousseaux, Maxime W C" sort="Rousseaux, Maxime W C" uniqKey="Rousseaux M" first="Maxime W. C." last="Rousseaux">Maxime W. C. Rousseaux</name><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name></country><country name="Pays-Bas"><noRegion><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name></noRegion></country><country name="Corée du Sud"><noRegion><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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