Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress
Identifieur interne : 000C42 ( Pmc/Checkpoint ); précédent : 000C41; suivant : 000C43Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress
Auteurs : Raymond H. Kim [Canada] ; Patrice D. Smith [Canada] ; Hossein Aleyasin [Canada] ; Shawn Hayley [Canada] ; Matthew P. Mount [Canada] ; Scott Pownall [Canada] ; Andrew Wakeham [Canada] ; Annick J. You-Ten [Canada] ; Suneil K. Kalia [Canada] ; Patrick Horne [Canada] ; David Westaway [Canada] ; Andres M. Lozano [Canada] ; Hymie Anisman [Canada] ; David S. Park [Canada] ; Tak W. Mak [Canada]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2005.
Abstract
Mutations of the
Url:
DOI: 10.1073/pnas.0501282102
PubMed: 15784737
PubMed Central: 555037
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress</title><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="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Smith, Patrice D" sort="Smith, Patrice D" uniqKey="Smith P" first="Patrice D." last="Smith">Patrice D. Smith</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><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="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff><country>Canada</country><wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Mount, Matthew P" sort="Mount, Matthew P" uniqKey="Mount M" first="Matthew P." last="Mount">Matthew P. Mount</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Pownall, Scott" sort="Pownall, Scott" uniqKey="Pownall S" first="Scott" last="Pownall">Scott Pownall</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">enGene Incorporated, Vancouver, BC, Canada V6T 1Z3;</nlm:aff><country>Canada</country><wicri:regionArea>enGene Incorporated, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Wakeham, Andrew" sort="Wakeham, Andrew" uniqKey="Wakeham A" first="Andrew" last="Wakeham">Andrew Wakeham</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="You Ten, Annick J" sort="You Ten, Annick J" uniqKey="You Ten A" first="Annick J." last="You-Ten">Annick J. You-Ten</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff><country>Canada</country><wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Horne, Patrick" sort="Horne, Patrick" uniqKey="Horne P" first="Patrick" last="Horne">Patrick Horne</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff><country>Canada</country><wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff><country>Canada</country><wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff><country>Canada</country><wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff><country>Canada</country><wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></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="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></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="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15784737</idno><idno type="pmc">555037</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC555037</idno><idno type="RBID">PMC:555037</idno><idno type="doi">10.1073/pnas.0501282102</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">000319</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000319</idno><idno type="wicri:Area/Pmc/Curation">000319</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000319</idno><idno type="wicri:Area/Pmc/Checkpoint">000C42</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C42</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress</title><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="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Smith, Patrice D" sort="Smith, Patrice D" uniqKey="Smith P" first="Patrice D." last="Smith">Patrice D. Smith</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><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="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff><country>Canada</country><wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Mount, Matthew P" sort="Mount, Matthew P" uniqKey="Mount M" first="Matthew P." last="Mount">Matthew P. Mount</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Pownall, Scott" sort="Pownall, Scott" uniqKey="Pownall S" first="Scott" last="Pownall">Scott Pownall</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">enGene Incorporated, Vancouver, BC, Canada V6T 1Z3;</nlm:aff><country>Canada</country><wicri:regionArea>enGene Incorporated, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Wakeham, Andrew" sort="Wakeham, Andrew" uniqKey="Wakeham A" first="Andrew" last="Wakeham">Andrew Wakeham</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="You Ten, Annick J" sort="You Ten, Annick J" uniqKey="You Ten A" first="Annick J." last="You-Ten">Annick J. You-Ten</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff><country>Canada</country><wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Horne, Patrick" sort="Horne, Patrick" uniqKey="Horne P" first="Patrick" last="Horne">Patrick Horne</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff><country>Canada</country><wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name><affiliation wicri:level="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</nlm:aff><country>Canada</country><wicri:regionArea>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x98a91e0.0x9eb80d0">Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8</nlm:aff><country>Canada</country><wicri:regionArea>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name><affiliation wicri:level="1"><nlm:aff id="N0x98a91e0.0x9eb80d0">Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;</nlm:aff><country>Canada</country><wicri:regionArea>Institute for Neuroscience, Carleton University, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></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="N0x98a91e0.0x9eb80d0">Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></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="4"><nlm:aff id="N0x98a91e0.0x9eb80d0">Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;</nlm:aff><country>Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></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="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mutations of the <italic>DJ-1</italic> (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the <italic>substantia nigra</italic> and fiber densities and dopamine levels in the striatum were normal. However, DJ-1–/– mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1–/–embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1–/– mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress <italic>in vitro</italic>. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="publisher-id">pnas</journal-id><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">15784737</article-id><article-id pub-id-type="pmc">555037</article-id><article-id pub-id-type="publisher-id">01025215</article-id><article-id pub-id-type="doi">10.1073/pnas.0501282102</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Neuroscience</subject></subj-group></subj-group></article-categories><title-group><article-title>Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Raymond H.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">*</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Patrice D.</given-names></name><xref ref-type="fn" rid="fn1">†</xref><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">‡</xref></contrib><contrib contrib-type="author"><name><surname>Aleyasin</surname><given-names>Hossein</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">‡</xref></contrib><contrib contrib-type="author"><name><surname>Hayley</surname><given-names>Shawn</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">§</xref></contrib><contrib contrib-type="author"><name><surname>Mount</surname><given-names>Matthew P.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">‡</xref></contrib><contrib contrib-type="author"><name><surname>Pownall</surname><given-names>Scott</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">¶</xref></contrib><contrib contrib-type="author"><name><surname>Wakeham</surname><given-names>Andrew</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">*</xref></contrib><contrib contrib-type="author"><name><surname>You-Ten</surname><given-names>Annick J.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">*</xref></contrib><contrib contrib-type="author"><name><surname>Kalia</surname><given-names>Suneil K.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">∥</xref></contrib><contrib contrib-type="author"><name><surname>Horne</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">**</xref></contrib><contrib contrib-type="author"><name><surname>Westaway</surname><given-names>David</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">**</xref></contrib><contrib contrib-type="author"><name><surname>Lozano</surname><given-names>Andres M.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">∥</xref></contrib><contrib contrib-type="author"><name><surname>Anisman</surname><given-names>Hymie</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">§</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>David S.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">‡</xref><xref ref-type="fn" rid="fn2">††</xref><xref ref-type="corresp" rid="cor1">‡‡</xref></contrib><contrib contrib-type="author"><name><surname>Mak</surname><given-names>Tak W.</given-names></name><xref ref-type="aff" rid="N0x98a91e0.0x9eb80d0">*</xref><xref ref-type="fn" rid="fn2">††</xref><xref ref-type="corresp" rid="cor1">‡‡</xref></contrib></contrib-group><aff id="N0x98a91e0.0x9eb80d0"><label>*</label>Campbell Family Institute for Breast Cancer Research, Advanced Medical Discovery Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;<label>‡</label>Neuroscience Research Group, Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada K1H 8M5;<label>§</label>Institute for Neuroscience, Carleton University, Ottawa, ON, Canada K1H 6N5;<label>¶</label>enGene Incorporated, Vancouver, BC, Canada V6T 1Z3;<label>∥</label>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, Toronto, ON, Canada M5T 2S8; and<label>**</label>Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2</aff><author-notes><fn id="cor1"><label>‡‡</label><p> To whom correspondence may be addressed. E-mail: <email>dpark@uottawa.ca</email> or <email>tmak@uhnres.utoronto.ca</email>. </p></fn><fn id="fn1"><label>†</label><p>R.H.K. and P.D.S. contributed equally to this work.</p></fn><fn id="fn2"><label>††</label><p>D.S.P. and T.W.M. contributed equally to this work.</p></fn><fn><p>Contributed by Tak W. Mak, February 16, 2005</p></fn></author-notes><pub-date pub-type="ppub"><day>5</day><month>4</month><year>2005</year></pub-date><pub-date pub-type="epub"><day>22</day><month>3</month><year>2005</year></pub-date><volume>102</volume><issue>14</issue><fpage>5215</fpage><lpage>5220</lpage><copyright-statement>Copyright © 2005, The National Academy of Sciences</copyright-statement><copyright-year>2005</copyright-year><license><p>Freely available online through the PNAS open access option.</p></license><abstract><p>Mutations of the <italic>DJ-1</italic> (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the <italic>substantia nigra</italic> and fiber densities and dopamine levels in the striatum were normal. However, DJ-1–/– mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1–/–embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1–/– mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress <italic>in vitro</italic>. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.</p></abstract></article-meta><notes><fn-group><fn><p>Author contributions: R.H.K., P.D.S., H. Aleyasin, S.H., S.P., S.K.K., D.W., A.M.L., D.S.P., and T.W.M. designed research; R.H.K., P.D.S., H. Aleyasin, S.H., M.P.M., A.W., A.J.Y.-T., and H. Anisman performed research; P.H. contributed new reagents/analytic tools; R.H.K. and D.S.P. analyzed data; and R.H.K. and D.S.P. wrote the paper.</p></fn><fn><p>Abbreviations: MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine; MPP+, active metabolite of MPTP; PD, Parkinson's disease; SNc, <italic>substantia nigra pars compacta</italic>; TH, tyrosine hydroxylase; DAT, dopamine transporter protein.</p></fn></fn-group></notes></front></pmc><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Kim, Raymond H" sort="Kim, Raymond H" uniqKey="Kim R" first="Raymond H." last="Kim">Raymond H. Kim</name></region><name sortKey="Aleyasin, Hossein" sort="Aleyasin, Hossein" uniqKey="Aleyasin H" first="Hossein" last="Aleyasin">Hossein Aleyasin</name><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><name sortKey="Horne, Patrick" sort="Horne, Patrick" uniqKey="Horne P" first="Patrick" last="Horne">Patrick Horne</name><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><name sortKey="Mount, Matthew P" sort="Mount, Matthew P" uniqKey="Mount M" first="Matthew P." last="Mount">Matthew P. Mount</name><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><name sortKey="Pownall, Scott" sort="Pownall, Scott" uniqKey="Pownall S" first="Scott" last="Pownall">Scott Pownall</name><name sortKey="Smith, Patrice D" sort="Smith, Patrice D" uniqKey="Smith P" first="Patrice D." last="Smith">Patrice D. Smith</name><name sortKey="Wakeham, Andrew" sort="Wakeham, Andrew" uniqKey="Wakeham A" first="Andrew" last="Wakeham">Andrew Wakeham</name><name sortKey="Westaway, David" sort="Westaway, David" uniqKey="Westaway D" first="David" last="Westaway">David Westaway</name><name sortKey="You Ten, Annick J" sort="You Ten, Annick J" uniqKey="You Ten A" first="Annick J." last="You-Ten">Annick J. You-Ten</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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