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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></affiliation></author><author><name sortKey="Irrcher, Isabella" sort="Irrcher, Isabella" uniqKey="Irrcher I" first="Isabella" last="Irrcher">Isabella Irrcher</name><affiliation><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></affiliation></author><author><name sortKey="Parsanejad, Mohammad" sort="Parsanejad, Mohammad" uniqKey="Parsanejad M" first="Mohammad" last="Parsanejad">Mohammad Parsanejad</name><affiliation><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff2"><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</nlm:aff></affiliation></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><affiliation><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></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</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">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff2"><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</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">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></affiliation><affiliation><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></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></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></affiliation></author><author><name sortKey="Irrcher, Isabella" sort="Irrcher, Isabella" uniqKey="Irrcher I" first="Isabella" last="Irrcher">Isabella Irrcher</name><affiliation><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></affiliation></author><author><name sortKey="Parsanejad, Mohammad" sort="Parsanejad, Mohammad" uniqKey="Parsanejad M" first="Mohammad" last="Parsanejad">Mohammad Parsanejad</name><affiliation><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff2"><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</nlm:aff></affiliation></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><affiliation><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></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><nlm:aff id="aff1">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</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">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></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><nlm:aff id="aff2"><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</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">Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</nlm:aff></affiliation><affiliation><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></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></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><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="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><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">20133695</article-id><article-id pub-id-type="pmc">2840364</article-id><article-id pub-id-type="publisher-id">200914876</article-id><article-id pub-id-type="doi">10.1073/pnas.0914876107</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>DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Aleyasin</surname><given-names>Hossein</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rousseaux</surname><given-names>Maxime W. C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marcogliese</surname><given-names>Paul C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hewitt</surname><given-names>Sarah J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Irrcher</surname><given-names>Isabella</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Joselin</surname><given-names>Alvin P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Parsanejad</surname><given-names>Mohammad</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Raymond H.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rizzu</surname><given-names>Patrizia</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Callaghan</surname><given-names>Steve M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</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>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mak</surname><given-names>Tak W.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</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>a</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1"><sup>a</sup>Department of Cellular and Molecular Medicine,<institution>University of Ottawa</institution>, Ottawa, ON K1H 8M5,<country>Canada</country>;</aff><aff id="aff2"><sup>b</sup><institution>Campbell Family Institute for Breast Cancer Research</institution>, Toronto, ON M5G 2C1,<country>Canada</country>;</aff><aff id="aff3"><sup>c</sup>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>; and</aff><aff id="aff4"><sup>d</sup>Department of Cogno-Mechatronics Engineering,<institution>Pusan National University</institution>, Geumjeong GU, Busan 609 735<country>South Korea</country></aff></contrib-group><author-notes><corresp id="cor1"><sup>2</sup>To whom correspondence should be addressed. E-mail: <email>dpark@uottawa.ca</email> or <email>tmak@uhnresearch.ca</email>.</corresp><fn fn-type="edited-by"><p>Contributed by Tak Wah Mak, December 24, 2009 (sent for review December 15, 2009)</p></fn><fn fn-type="con"><p>Author contributions: H.A., M.W.C.R., R.H.K., R.S.S., T.W.M., and D.S.P. designed research; H.A., M.W.C.R., P.C.M., S.J.H., I.I., A.P.J., and M.P. performed research; R.H.K., P.R., S.C., R.S.S., and T.W.M. contributed new reagents/analytic tools; H.A., M.W.C.R., P.C.M., S.J.H., A.P.J., M.P., and D.S.P. analyzed data; and H.A., M.W.C.R., I.I., and D.S.P. wrote the paper.</p></fn><fn fn-type="equal" id="fn1"><p><sup>1</sup>H.A. and M.W.C.R. contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>26</day><month>1</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>16</day><month>2</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>26</day><month>1</month><year>2010</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>107</volume><issue>7</issue><fpage>3186</fpage><lpage>3191</lpage><permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.200914876.pdf"></self-uri><abstract><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></abstract><kwd-group><kwd>neurodegeneration</kwd><kwd>Parkinson disease</kwd><kwd>reactive oxygen species</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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