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Article: Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity

TitleMitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity
Authors
KeywordsDopamine
Free radicals
Mitochondrial dysfunction
MPP+
Neuroprotection
Oxidative stress
Parkinson disease
Uncoupling proteins
Issue Date2010
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed
Citation
Free Radical Biology And Medicine, 2010, v. 49 n. 6, p. 1023-1035 How to Cite?
AbstractWe explored the protective mechanisms of human neuronal mitochondrial uncoupling protein-5 (UCP5) in MPP+- and dopamine-induced toxicity after its stable overexpression in SH-SY5Y cells. We raised specific polyclonal antibodies. Overexpressed UCP5 localized in mitochondria but not in cytosol. UCP5 overexpression increased proton leak, decreased mitochondrial membrane potential (MMP), reduced ATP production, and increased overall oxygen consumption (demonstrating uncoupling activity). UCP5 overexpression did not affect other neuronal UCP expression (UCP2 and UCP4). Overexpressing UCP5 is protective against MPP+- and dopamine-induced toxicity. MPP+ and dopamine exposure for 6h reduced MMP and increased superoxide levels. ATP levels in UCP5-overexpressing cells were preserved under MPP+ and dopamine toxicity, comparable to levels in untreated vector controls. At 24h, UCP5 overexpression preserved MMP, ATP levels, and cell survival; attenuated superoxide generation; and maintained oxidative phosphorylation as indicated by lower lactate levels. MPP+ and dopamine exposure induced UCP5 mRNA transcription but did not decrease transcript degradation, as inhibition of transcription by actinomycin-D abolished induction by either toxin. Compared with our previous studies on UCP4, we observed functional differences between UCP4 and UCP5 in enhancing mitochondrial efficiency. These neuronal UCP homologues may work synergistically to maintain oxidative balance (through uncoupling activities) and ATP production (by modifying MMP). © 2010 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/163329
ISSN
2015 Impact Factor: 5.784
2015 SCImago Journal Rankings: 2.468
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKwok, KHHen_HK
dc.contributor.authorHo, PWLen_HK
dc.contributor.authorChu, ACYen_HK
dc.contributor.authorHo, JWMen_HK
dc.contributor.authorLiu, HFen_HK
dc.contributor.authorYiu, DCWen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorKung, MHWen_HK
dc.contributor.authorRamsden, DBen_HK
dc.contributor.authorHo, SLen_HK
dc.date.accessioned2012-09-05T05:30:06Z-
dc.date.available2012-09-05T05:30:06Z-
dc.date.issued2010en_HK
dc.identifier.citationFree Radical Biology And Medicine, 2010, v. 49 n. 6, p. 1023-1035en_HK
dc.identifier.issn0891-5849en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163329-
dc.description.abstractWe explored the protective mechanisms of human neuronal mitochondrial uncoupling protein-5 (UCP5) in MPP+- and dopamine-induced toxicity after its stable overexpression in SH-SY5Y cells. We raised specific polyclonal antibodies. Overexpressed UCP5 localized in mitochondria but not in cytosol. UCP5 overexpression increased proton leak, decreased mitochondrial membrane potential (MMP), reduced ATP production, and increased overall oxygen consumption (demonstrating uncoupling activity). UCP5 overexpression did not affect other neuronal UCP expression (UCP2 and UCP4). Overexpressing UCP5 is protective against MPP+- and dopamine-induced toxicity. MPP+ and dopamine exposure for 6h reduced MMP and increased superoxide levels. ATP levels in UCP5-overexpressing cells were preserved under MPP+ and dopamine toxicity, comparable to levels in untreated vector controls. At 24h, UCP5 overexpression preserved MMP, ATP levels, and cell survival; attenuated superoxide generation; and maintained oxidative phosphorylation as indicated by lower lactate levels. MPP+ and dopamine exposure induced UCP5 mRNA transcription but did not decrease transcript degradation, as inhibition of transcription by actinomycin-D abolished induction by either toxin. Compared with our previous studies on UCP4, we observed functional differences between UCP4 and UCP5 in enhancing mitochondrial efficiency. These neuronal UCP homologues may work synergistically to maintain oxidative balance (through uncoupling activities) and ATP production (by modifying MMP). © 2010 Elsevier Inc.en_HK
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomeden_HK
dc.relation.ispartofFree Radical Biology and Medicineen_HK
dc.subjectDopamineen_HK
dc.subjectFree radicalsen_HK
dc.subjectMitochondrial dysfunctionen_HK
dc.subjectMPP+en_HK
dc.subjectNeuroprotectionen_HK
dc.subjectOxidative stressen_HK
dc.subjectParkinson diseaseen_HK
dc.subjectUncoupling proteinsen_HK
dc.subject.mesh1-Methyl-4-Phenylpyridinium - Toxicityen_US
dc.subject.meshAdenosine Triphosphate - Metabolismen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Survivalen_US
dc.subject.meshCytoprotectionen_US
dc.subject.meshDopamine - Pharmacologyen_US
dc.subject.meshGlycolysis - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Potential, Mitochondrial - Drug Effectsen_US
dc.subject.meshMembrane Transport Proteins - Genetics - Metabolismen_US
dc.subject.meshMitochondria - Drug Effects - Metabolismen_US
dc.subject.meshNerve Tissue Proteins - Genetics - Metabolismen_US
dc.subject.meshNeurons - Drug Effects - Metabolism - Pathologyen_US
dc.subject.meshOxidative Stress - Drug Effectsen_US
dc.subject.meshSuperoxides - Metabolismen_US
dc.subject.meshTransgenes - Geneticsen_US
dc.titleMitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicityen_HK
dc.typeArticleen_HK
dc.identifier.emailHo, PWL: hwl2002@hku.hken_HK
dc.identifier.emailChu, ACY: bcccy@hkucc.hku.hken_HK
dc.identifier.emailHo, SL: slho@hku.hken_HK
dc.identifier.authorityHo, PWL=rp00259en_HK
dc.identifier.authorityChu, ACY=rp00505en_HK
dc.identifier.authorityHo, SL=rp00240en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.freeradbiomed.2010.06.017en_HK
dc.identifier.pmid20600837-
dc.identifier.scopuseid_2-s2.0-77955514244en_HK
dc.identifier.hkuros170991-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955514244&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1023en_HK
dc.identifier.epage1035en_HK
dc.identifier.eissn1873-4596-
dc.identifier.isiWOS:000281047000009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKwok, KHH=7102194193en_HK
dc.identifier.scopusauthoridHo, PWL=25027612100en_HK
dc.identifier.scopusauthoridChu, ACY=24343085700en_HK
dc.identifier.scopusauthoridHo, JWM=8685214100en_HK
dc.identifier.scopusauthoridLiu, HF=27170235100en_HK
dc.identifier.scopusauthoridYiu, DCW=36674071000en_HK
dc.identifier.scopusauthoridChan, KH=7406034963en_HK
dc.identifier.scopusauthoridKung, MHW=36336960300en_HK
dc.identifier.scopusauthoridRamsden, DB=7102612805en_HK
dc.identifier.scopusauthoridHo, SL=25959633500en_HK
dc.identifier.citeulike7419244-

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