Inactivation of Pink1 Gene in Vivo Sensitizes Dopamine-producing Neurons to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Can Be Rescued by Autosomal Recessive Parkinson Disease Genes, Parkin or DJ-1
Identifieur interne : 000565 ( Pmc/Curation ); précédent : 000564; suivant : 000566Inactivation of Pink1 Gene in Vivo Sensitizes Dopamine-producing Neurons to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Can Be Rescued by Autosomal Recessive Parkinson Disease Genes, Parkin or DJ-1
Auteurs : M. Emdadul Haque ; Matthew P. Mount ; Farzaneh Safarpour ; Elizabeth Abdel-Messih ; Steve Callaghan ; Chantal Mazerolle ; Tohru Kitada ; Ruth S. Slack ; Valerie Wallace ; Jie Shen ; Hymie Anisman ; David S. ParkSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2012.
Abstract
Url:
DOI: 10.1074/jbc.M112.346437
PubMed: 22511790
PubMed Central: 3391096
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inactivation of <italic>Pink1</italic> Gene <italic>in Vivo</italic> Sensitizes Dopamine-producing Neurons to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Can Be Rescued by Autosomal Recessive Parkinson Disease Genes, <italic>Parkin</italic> or <italic>DJ-1</italic></title><author><name sortKey="Haque, M Emdadul" sort="Haque, M Emdadul" uniqKey="Haque M" first="M. Emdadul" last="Haque">M. Emdadul Haque</name><affiliation><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Safarpour, Farzaneh" sort="Safarpour, Farzaneh" uniqKey="Safarpour F" first="Farzaneh" last="Safarpour">Farzaneh Safarpour</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Abdel Messih, Elizabeth" sort="Abdel Messih, Elizabeth" uniqKey="Abdel Messih E" first="Elizabeth" last="Abdel-Messih">Elizabeth Abdel-Messih</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Callaghan, Steve" sort="Callaghan, Steve" uniqKey="Callaghan S" first="Steve" last="Callaghan">Steve Callaghan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Mazerolle, Chantal" sort="Mazerolle, Chantal" uniqKey="Mazerolle C" first="Chantal" last="Mazerolle">Chantal Mazerolle</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kitada, Tohru" sort="Kitada, Tohru" uniqKey="Kitada T" first="Tohru" last="Kitada">Tohru Kitada</name><affiliation><nlm:aff id="aff2"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wallace, Valerie" sort="Wallace, Valerie" uniqKey="Wallace V" first="Valerie" last="Wallace">Valerie Wallace</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Shen, Jie" sort="Shen, Jie" uniqKey="Shen J" first="Jie" last="Shen">Jie Shen</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name><affiliation><nlm:aff id="aff4"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22511790</idno><idno type="pmc">3391096</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391096</idno><idno type="RBID">PMC:3391096</idno><idno type="doi">10.1074/jbc.M112.346437</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000565</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000565</idno><idno type="wicri:Area/Pmc/Curation">000565</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000565</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Inactivation of <italic>Pink1</italic> Gene <italic>in Vivo</italic> Sensitizes Dopamine-producing Neurons to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Can Be Rescued by Autosomal Recessive Parkinson Disease Genes, <italic>Parkin</italic> or <italic>DJ-1</italic></title><author><name sortKey="Haque, M Emdadul" sort="Haque, M Emdadul" uniqKey="Haque M" first="M. Emdadul" last="Haque">M. Emdadul Haque</name><affiliation><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Safarpour, Farzaneh" sort="Safarpour, Farzaneh" uniqKey="Safarpour F" first="Farzaneh" last="Safarpour">Farzaneh Safarpour</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Abdel Messih, Elizabeth" sort="Abdel Messih, Elizabeth" uniqKey="Abdel Messih E" first="Elizabeth" last="Abdel-Messih">Elizabeth Abdel-Messih</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Callaghan, Steve" sort="Callaghan, Steve" uniqKey="Callaghan S" first="Steve" last="Callaghan">Steve Callaghan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Mazerolle, Chantal" sort="Mazerolle, Chantal" uniqKey="Mazerolle C" first="Chantal" last="Mazerolle">Chantal Mazerolle</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kitada, Tohru" sort="Kitada, Tohru" uniqKey="Kitada T" first="Tohru" last="Kitada">Tohru Kitada</name><affiliation><nlm:aff id="aff2"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wallace, Valerie" sort="Wallace, Valerie" uniqKey="Wallace V" first="Valerie" last="Wallace">Valerie Wallace</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Shen, Jie" sort="Shen, Jie" uniqKey="Shen J" first="Jie" last="Shen">Jie Shen</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Anisman, Hymie" sort="Anisman, Hymie" uniqKey="Anisman H" first="Hymie" last="Anisman">Hymie Anisman</name><affiliation><nlm:aff id="aff4"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Mutations in <italic>Pink1</italic> are associated with Parkinson disease.</p><p><bold>Results:</bold> Mouse <italic>Pink1</italic> deficiency results in hypersensitivity to MPTP-induced dopaminergic neuronal loss, which can be rescued with expression of human <italic>Parkin</italic> or <italic>DJ-1</italic>.</p><p><bold>Conclusion:</bold><italic>Pink1</italic> gene can regulate response to exogenous stress.</p><p><bold>Significance:</bold> These results indicate how endogenous <italic>Pink1</italic> plays an important role in management of exogenous stress in mouse brain.</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">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22511790</article-id><article-id pub-id-type="pmc">3391096</article-id><article-id pub-id-type="publisher-id">M112.346437</article-id><article-id pub-id-type="doi">10.1074/jbc.M112.346437</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neurobiology</subject></subj-group></article-categories><title-group><article-title>Inactivation of <italic>Pink1</italic> Gene <italic>in Vivo</italic> Sensitizes Dopamine-producing Neurons to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Can Be Rescued by Autosomal Recessive Parkinson Disease Genes, <italic>Parkin</italic> or <italic>DJ-1</italic></article-title><alt-title alt-title-type="short">Pink1 Deficiency Potentiates MPTP Toxicity</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Haque</surname><given-names>M. Emdadul</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mount</surname><given-names>Matthew P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Safarpour</surname><given-names>Farzaneh</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Abdel-Messih</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Callaghan</surname><given-names>Steve</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mazerolle</surname><given-names>Chantal</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kitada</surname><given-names>Tohru</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Slack</surname><given-names>Ruth S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wallace</surname><given-names>Valerie</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shen</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Anisman</surname><given-names>Hymie</given-names></name><xref ref-type="aff" rid="aff4"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>David S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff5">**</xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada</aff><aff id="aff2">the<label>§</label>Ottawa Hospital Research Institute, Ottawa, Ontario K1Y 4E9, Canada,</aff><aff id="aff3">the<label>¶</label>Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115,</aff><aff id="aff4">the<label>‖</label>Institute for Neuroscience, Carleton University, Ottawa, Ontario K1H 6N5, Canada, and</aff><aff id="aff5">the<label>**</label>Department of Cogno-Mechatronics Engineering, Pusan National University, Pusan 609-735, Korea</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> Supported by grants from Neuroscience Canada, Canadian Institute of Health Research, Heart and Stroke Foundation, Ontario, Centre for Stroke Recovery, Parkinson's Disease Foundation, Parkinson's Society Canada, Parkinson's Research Consortium, Centres of Excellence in Neurodegeneration (COEN), and World Class University program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, South Korea, Grant R31-2008-000-20004-0. Holder of a Career Scientist award from the Heart and Stroke Foundation Ontario. To whom correspondence should be addressed: <addr-line>Dept. of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Rd., Ottawa, ON K1H 8M5, Canada.</addr-line> Tel.: <phone>613-562-5800 (ext. 8816)</phone>; Fax: <fax>613-562-5403</fax>; E-mail: <email>dpark@uottawa.ca</email>.</corresp><fn fn-type="other" id="FN1"><label>1</label><p>Recipient of Canadian Institute of Health Research Training Program in Neurodegenerative Lipidomics.</p></fn></author-notes><pub-date pub-type="ppub"><day>29</day><month>6</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>17</day><month>4</month><year>2012</year></pub-date><volume>287</volume><issue>27</issue><fpage>23162</fpage><lpage>23170</lpage><history><date date-type="received"><day>26</day><month>1</month><year>2012</year></date><date date-type="rev-recd"><day>21</day><month>3</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2012</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc02712023162.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> Mutations in <italic>Pink1</italic> are associated with Parkinson disease.</p><p><bold>Results:</bold> Mouse <italic>Pink1</italic> deficiency results in hypersensitivity to MPTP-induced dopaminergic neuronal loss, which can be rescued with expression of human <italic>Parkin</italic> or <italic>DJ-1</italic>.</p><p><bold>Conclusion:</bold><italic>Pink1</italic> gene can regulate response to exogenous stress.</p><p><bold>Significance:</bold> These results indicate how endogenous <italic>Pink1</italic> plays an important role in management of exogenous stress in mouse brain.</p></abstract><abstract><p>Mutations in the mitochondrial PTEN-induced kinase 1 (<italic>Pink1</italic>) gene have been linked to Parkinson disease (PD). Recent reports including our own indicated that ectopic <italic>Pink1</italic> expression is protective against toxic insult <italic>in vitro</italic>, suggesting a potential role for endogenous <italic>Pink1</italic> in mediating survival. However, the role of endogenous <italic>Pink1</italic> in survival, particularly <italic>in vivo</italic>, is unclear. To address this critical question, we examined whether down-regulation of <italic>Pink1</italic> affects dopaminergic neuron loss following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the adult mouse. Two model systems were utilized: virally delivered shRNA-mediated knockdown of <italic>Pink1</italic> and germ line-deficient mice. In both instances, loss of <italic>Pink1</italic> generated significant sensitivity to damage induced by systemic MPTP treatment. This sensitivity was associated with greater loss of dopaminergic neurons in the Substantia Nigra pars compacta and terminal dopamine fiber density in the striatum region. Importantly, we also show that viral mediated expression of two other recessive PD-linked familial genes, <italic>DJ-1</italic> and <italic>Parkin</italic>, can protect dopaminergic neurons even in the absence of <italic>Pink1</italic>. This evidence not only provides strong evidence for the role of endogenous <italic>Pink1</italic> in neuronal survival, but also supports a role of <italic>DJ-1</italic> and <italic>Parkin</italic> acting parallel or downstream of endogenous <italic>Pink1</italic> to mediate survival in a mammalian <italic>in vivo</italic> context.</p></abstract><kwd-group><kwd><italic>DJ-1</italic></kwd><kwd>Neurodegeneration</kwd><kwd><italic>Parkin</italic></kwd><kwd>Parkinson Disease</kwd><kwd><italic>Pink1</italic></kwd><kwd>MPTP</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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