DJ‐1 modulates the expression of Cu/Zn‐superoxide dismutase‐1 through the Erk1/2–Elk1 pathway in neuroprotection
Identifieur interne : 001A97 ( Main/Curation ); précédent : 001A96; suivant : 001A98DJ‐1 modulates the expression of Cu/Zn‐superoxide dismutase‐1 through the Erk1/2–Elk1 pathway in neuroprotection
Auteurs : Zhiquan Wang [République populaire de Chine] ; Jun Liu [République populaire de Chine] ; Siyan Chen [République populaire de Chine] ; Ying Wang [République populaire de Chine] ; Li Cao [République populaire de Chine] ; Yu Zhang [République populaire de Chine] ; Wenyan Kang [République populaire de Chine] ; Hui Li [République populaire de Chine] ; Yaxing Gui [République populaire de Chine] ; Shengdi Chen [République populaire de Chine] ; Jianqing Ding [République populaire de Chine]Source :
- Annals of Neurology [ 0364-5134 ] ; 2011-10.
Abstract
Objective:: Loss of function mutations of Park7/DJ‐1 gene increase the susceptibility of dopaminergic cells to reactive oxygen species and cause early onset familial Parkinson disease (PD). However, the mechanisms underlying dopaminergic neuron loss related to DJ‐1 mutation remain undefined. Therefore, it is important to find the new mechanisms underlying the antioxidative functions of DJ‐1. Methods:: DJ‐1 knockdown cells and DJ‐1 knockout mice were used to elucidate the mechanisms underlying the antioxidative stress of DJ‐1. Preliminary study of the saliva from PD patients and controls was used to confirm our findings obtained from the above studies. Results:: Our experiments showed that DJ‐1 interacted with Erk1/2 and was required for the nuclear translocation of Erk1/2 upon oxidative stimulation. The translocation of Erk1/2 activated Elk1 and sequentially promoted superoxide dismutase1 (SOD1) expression. The nuclear translocation of Erk1/2, the activation of Elk1, and the ensuing upregulation of SOD1 were all suppressed in DJ‐1 knockdown cells and DJ‐1 null mice treated with oxidative insult. Furthermore, reintroduction of SOD1 into DJ‐1 knockdown cells protected them against oxidative stress. Finally, in the preliminary study, we found close correlation between the protein levels of DJ‐1 and SOD1 in the saliva samples from different stages of PD patients. Interpretation:: Our studies suggest that DJ‐1 regulates SOD1 expression through Erk1/2–Elk1 pathway in its protective response to oxidative insult. ANN NEUROL 2011
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DOI: 10.1002/ana.22514
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Shengdi Chen<affiliation><mods:affiliation>Shengdi Chen, Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. ChinaJianqing Ding, Institute of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai 200025 P.R. China</mods:affiliation><wicri:noCountry code="subField">Shanghai 200025 P.R. China</wicri:noCountry></affiliation><affiliation><mods:affiliation>Shengdi Chen, Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. ChinaJianqing Ding, Institute of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai 200025 P.R. China</mods:affiliation><wicri:noCountry code="subField">Shanghai 200025 P.R. China</wicri:noCountry></affiliation>Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">DJ‐1 modulates the expression of Cu/Zn‐superoxide dismutase‐1 through the Erk1/2–Elk1 pathway in neuroprotection</title><author><name sortKey="Wang, Zhiquan" sort="Wang, Zhiquan" uniqKey="Wang Z" first="Zhiquan" last="Wang">Zhiquan Wang</name><affiliation wicri:level="1"><mods:affiliation>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Graduate School of the Chinese Academy of Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Graduate School of the Chinese Academy of Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Siyan" sort="Chen, Siyan" uniqKey="Chen S" first="Siyan" last="Chen">Siyan Chen</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Li" sort="Cao, Li" uniqKey="Cao L" first="Li" last="Cao">Li Cao</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Kang, Wenyan" sort="Kang, Wenyan" uniqKey="Kang W" first="Wenyan" last="Kang">Wenyan Kang</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Li, Hui" sort="Li, Hui" uniqKey="Li H" first="Hui" last="Li">Hui Li</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Gui, Yaxing" sort="Gui, Yaxing" uniqKey="Gui Y" first="Yaxing" last="Gui">Yaxing Gui</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Shengdi" sort="Chen, Shengdi" uniqKey="Chen S" first="Shengdi" last="Chen">Shengdi Chen</name><affiliation wicri:level="1"><mods:affiliation>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation><affiliation><mods:affiliation>Shengdi Chen, Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. ChinaJianqing Ding, Institute of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai 200025 P.R. China</mods:affiliation><wicri:noCountry code="subField">Shanghai 200025 P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Ding, Jianqing" sort="Ding, Jianqing" uniqKey="Ding J" first="Jianqing" last="Ding">Jianqing Ding</name><affiliation wicri:level="1"><mods:affiliation>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation><affiliation><mods:affiliation>Shengdi Chen, Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. ChinaJianqing Ding, Institute of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai 200025 P.R. China</mods:affiliation><wicri:noCountry code="subField">Shanghai 200025 P.R. China</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:77B4307FAC153306CC0D47A044881E66E433C575</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1002/ana.22514</idno><idno type="url">https://api.istex.fr/document/77B4307FAC153306CC0D47A044881E66E433C575/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001D78</idno><idno type="wicri:Area/Main/Curation">001A97</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">DJ‐1 modulates the expression of Cu/Zn‐superoxide dismutase‐1 through the Erk1/2–Elk1 pathway in neuroprotection</title><author><name sortKey="Wang, Zhiquan" sort="Wang, Zhiquan" uniqKey="Wang Z" first="Zhiquan" last="Wang">Zhiquan Wang</name><affiliation wicri:level="1"><mods:affiliation>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Graduate School of the Chinese Academy of Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Graduate School of the Chinese Academy of Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Siyan" sort="Chen, Siyan" uniqKey="Chen S" first="Siyan" last="Chen">Siyan Chen</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Cao, Li" sort="Cao, Li" uniqKey="Cao L" first="Li" last="Cao">Li Cao</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Kang, Wenyan" sort="Kang, Wenyan" uniqKey="Kang W" first="Wenyan" last="Kang">Wenyan Kang</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Li, Hui" sort="Li, Hui" uniqKey="Li H" first="Hui" last="Li">Hui Li</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Gui, Yaxing" sort="Gui, Yaxing" uniqKey="Gui Y" first="Yaxing" last="Gui">Yaxing Gui</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Shengdi" sort="Chen, Shengdi" uniqKey="Chen S" first="Shengdi" last="Chen">Shengdi Chen</name><affiliation wicri:level="1"><mods:affiliation>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation><affiliation><mods:affiliation>Shengdi Chen, Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. ChinaJianqing Ding, Institute of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai 200025 P.R. China</mods:affiliation><wicri:noCountry code="subField">Shanghai 200025 P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Ding, Jianqing" sort="Ding, Jianqing" uniqKey="Ding J" first="Jianqing" last="Ding">Jianqing Ding</name><affiliation wicri:level="1"><mods:affiliation>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai, China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai</wicri:regionArea></affiliation><affiliation><mods:affiliation>Shengdi Chen, Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. ChinaJianqing Ding, Institute of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai 200025 P.R. China</mods:affiliation><wicri:noCountry code="subField">Shanghai 200025 P.R. China</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-10">2011-10</date><biblScope unit="volume">70</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="591">591</biblScope><biblScope unit="page" to="599">599</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">77B4307FAC153306CC0D47A044881E66E433C575</idno><idno type="DOI">10.1002/ana.22514</idno><idno type="ArticleID">ANA22514</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective:: Loss of function mutations of Park7/DJ‐1 gene increase the susceptibility of dopaminergic cells to reactive oxygen species and cause early onset familial Parkinson disease (PD). However, the mechanisms underlying dopaminergic neuron loss related to DJ‐1 mutation remain undefined. Therefore, it is important to find the new mechanisms underlying the antioxidative functions of DJ‐1. Methods:: DJ‐1 knockdown cells and DJ‐1 knockout mice were used to elucidate the mechanisms underlying the antioxidative stress of DJ‐1. Preliminary study of the saliva from PD patients and controls was used to confirm our findings obtained from the above studies. Results:: Our experiments showed that DJ‐1 interacted with Erk1/2 and was required for the nuclear translocation of Erk1/2 upon oxidative stimulation. The translocation of Erk1/2 activated Elk1 and sequentially promoted superoxide dismutase1 (SOD1) expression. The nuclear translocation of Erk1/2, the activation of Elk1, and the ensuing upregulation of SOD1 were all suppressed in DJ‐1 knockdown cells and DJ‐1 null mice treated with oxidative insult. Furthermore, reintroduction of SOD1 into DJ‐1 knockdown cells protected them against oxidative stress. Finally, in the preliminary study, we found close correlation between the protein levels of DJ‐1 and SOD1 in the saliva samples from different stages of PD patients. Interpretation:: Our studies suggest that DJ‐1 regulates SOD1 expression through Erk1/2–Elk1 pathway in its protective response to oxidative insult. ANN NEUROL 2011</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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