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Article: Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription

TitleProtection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription
Authors
Keywords3-Nitropropionic acid
Antioxidant response element
Astrocytes malonate
Issue Date2005
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 1, p. 244-249 How to Cite?
AbstractComplex II inhibitors 3-nitropropionic acid (3NP) and malonate cause striatal damage reminiscent of Huntington's disease and have been shown to involve oxidative stress in their pathogenesis. Because nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent transcriptional activation by means of the antioxidant response element is known to coordinate the up-regulation of cytoprotective genes involved in combating oxidative stress, we investigated the significance of Nrf2 in complex II-induced toxicity. We found that Nrf2-deficient cells and Nrf2 knockout mice are significantly more vulnerable to malonate and 3NP and demonstrate increased antioxidant response element (ARE)-regulated transcription mediated by astrocytes. Furthermore, ARE preactivation by means of intrastriatal transplantation of Nrf2-overexpressing astrocytes before lesioning conferred dramatic protection against complex II inhibition. These observations implicate Nrf2 as an essential inducible factor in the protection against complex II inhibitor-mediated neurotoxicity. These data also introduce Nrf2-mediated ARE transcription as a potential target of preventative therapy in neurodegenerative disorders such as Huntington's disease.
Persistent Identifierhttp://hdl.handle.net/10722/49046
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCalkins, MJen_HK
dc.contributor.authorJakel, RJen_HK
dc.contributor.authorJohnson, DAen_HK
dc.contributor.authorChan, Ken_HK
dc.contributor.authorYuen, WKen_HK
dc.contributor.authorJohnson, JAen_HK
dc.date.accessioned2008-06-12T06:33:14Z-
dc.date.available2008-06-12T06:33:14Z-
dc.date.issued2005en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 1, p. 244-249en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49046-
dc.description.abstractComplex II inhibitors 3-nitropropionic acid (3NP) and malonate cause striatal damage reminiscent of Huntington's disease and have been shown to involve oxidative stress in their pathogenesis. Because nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent transcriptional activation by means of the antioxidant response element is known to coordinate the up-regulation of cytoprotective genes involved in combating oxidative stress, we investigated the significance of Nrf2 in complex II-induced toxicity. We found that Nrf2-deficient cells and Nrf2 knockout mice are significantly more vulnerable to malonate and 3NP and demonstrate increased antioxidant response element (ARE)-regulated transcription mediated by astrocytes. Furthermore, ARE preactivation by means of intrastriatal transplantation of Nrf2-overexpressing astrocytes before lesioning conferred dramatic protection against complex II inhibition. These observations implicate Nrf2 as an essential inducible factor in the protection against complex II inhibitor-mediated neurotoxicity. These data also introduce Nrf2-mediated ARE transcription as a potential target of preventative therapy in neurodegenerative disorders such as Huntington's disease.en_HK
dc.format.extent386 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.rightsNational Academy of Sciences Proceedings. Copyright © National Academy of Sciences.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject3-Nitropropionic aciden_HK
dc.subjectAntioxidant response elementen_HK
dc.subjectAstrocytes malonateen_HK
dc.titleProtection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcriptionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=102&issue=1&spage=244&epage=249&date=2005&atitle=Protection+from+mitochondrial+complex+II+inhibition+in+vitro+and+in+vivo+by+Nrf2-mediated+transcriptionen_HK
dc.identifier.emailChan, K: kaimin@hkucc.hku.hken_HK
dc.identifier.authorityChan, K=rp00489en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1073/pnas.0408487101en_HK
dc.identifier.pmid15611470-
dc.identifier.pmcidPMC538748en_HK
dc.identifier.scopuseid_2-s2.0-11844253848en_HK
dc.identifier.hkuros113813-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-11844253848&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume102en_HK
dc.identifier.issue1en_HK
dc.identifier.spage244en_HK
dc.identifier.epage249en_HK
dc.identifier.isiWOS:000226216400044-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCalkins, MJ=7007180294en_HK
dc.identifier.scopusauthoridJakel, RJ=6602508857en_HK
dc.identifier.scopusauthoridJohnson, DA=7406822641en_HK
dc.identifier.scopusauthoridChan, K=7406032228en_HK
dc.identifier.scopusauthoridYuen, WK=7102761279en_HK
dc.identifier.scopusauthoridJohnson, JA=7406813149en_HK

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