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Article: Mitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stress

TitleMitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stress
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2003
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://stroke.ahajournals.org
Citation
Stroke, 2003, v. 34 n. 7, p. 1796-1802 How to Cite?
AbstractBackground and Purpose - Mitochondrial ATP-sensitive potassium (mitoKATP) channels are present in the brain, and several reports have shown that mitoKATP channel openers protect the brain against ischemic injury. However, the precise mechanisms of this protection are not well established. We hypothesized that mitoKATP channel openers prevent apoptosis by preserving mitochondrial membrane potential. Methods - We investigated the effect of mitoKATP channel openers on apoptosis induced by oxidative stress using cultured cerebellar granule neurons. Results - The mitoKATP channel opener diazoxide (100 μmol/L) significantly suppressed the number of cells with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive nuclei and the increase in caspase-3 activity induced by 20 μmol/L H2O2. Diazoxide and another opener, pinacidil, prevented the loss of mitochondrial inner membrane potential (ΔΨm) induced by H2O2. These effects were abolished by 5-hydroxydecanoate (500 μmol/L), a mitoKATP channel blocker. Cyclosporin A and bongkrekic acid, inhibitors of the mitochondrial permeability transition pore, also prevented ΔΨm loss, confirming the involvement of the mitochondrial permeability transition in the apoptotic cascade in neurons. Furthermore, diazoxide prevented the increase in extracellular glutamate concentration induced by H2O2, but this effect was not attributable to activation of surface KATP channels. Conclusions - MitoKATP channel openers inhibited apoptosis by preserving mitochondrial inner membrane potential. These beneficial effects may suggest a possible new target for neuroprotection.
Persistent Identifierhttp://hdl.handle.net/10722/91597
ISSN
2015 Impact Factor: 5.787
2015 SCImago Journal Rankings: 3.671
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTeshima, Yen_HK
dc.contributor.authorAkao, Men_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorChong, THen_HK
dc.contributor.authorBaumgartner, WAen_HK
dc.contributor.authorJohnston, MVen_HK
dc.contributor.authorMarbán, Een_HK
dc.date.accessioned2010-09-17T10:21:57Z-
dc.date.available2010-09-17T10:21:57Z-
dc.date.issued2003en_HK
dc.identifier.citationStroke, 2003, v. 34 n. 7, p. 1796-1802en_HK
dc.identifier.issn0039-2499en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91597-
dc.description.abstractBackground and Purpose - Mitochondrial ATP-sensitive potassium (mitoKATP) channels are present in the brain, and several reports have shown that mitoKATP channel openers protect the brain against ischemic injury. However, the precise mechanisms of this protection are not well established. We hypothesized that mitoKATP channel openers prevent apoptosis by preserving mitochondrial membrane potential. Methods - We investigated the effect of mitoKATP channel openers on apoptosis induced by oxidative stress using cultured cerebellar granule neurons. Results - The mitoKATP channel opener diazoxide (100 μmol/L) significantly suppressed the number of cells with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive nuclei and the increase in caspase-3 activity induced by 20 μmol/L H2O2. Diazoxide and another opener, pinacidil, prevented the loss of mitochondrial inner membrane potential (ΔΨm) induced by H2O2. These effects were abolished by 5-hydroxydecanoate (500 μmol/L), a mitoKATP channel blocker. Cyclosporin A and bongkrekic acid, inhibitors of the mitochondrial permeability transition pore, also prevented ΔΨm loss, confirming the involvement of the mitochondrial permeability transition in the apoptotic cascade in neurons. Furthermore, diazoxide prevented the increase in extracellular glutamate concentration induced by H2O2, but this effect was not attributable to activation of surface KATP channels. Conclusions - MitoKATP channel openers inhibited apoptosis by preserving mitochondrial inner membrane potential. These beneficial effects may suggest a possible new target for neuroprotection.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://stroke.ahajournals.orgen_HK
dc.relation.ispartofStrokeen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAdenosine Triphosphate - metabolism - pharmacologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosis - drug effects - physiologyen_HK
dc.subject.meshBongkrekic Acid - pharmacologyen_HK
dc.subject.meshCaspase 3en_HK
dc.subject.meshCaspases - metabolismen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCerebellum - cytologyen_HK
dc.subject.meshCyclosporine - pharmacologyen_HK
dc.subject.meshDiazoxide - pharmacologyen_HK
dc.subject.meshGlutamic Acid - metabolismen_HK
dc.subject.meshIon Channels - drug effects - metabolismen_HK
dc.subject.meshMembrane Potentials - drug effectsen_HK
dc.subject.meshMicroscopy, Confocalen_HK
dc.subject.meshMitochondria - drug effects - metabolismen_HK
dc.subject.meshMitochondrial Membrane Transport Proteinsen_HK
dc.subject.meshNeurons - cytology - drug effects - metabolismen_HK
dc.subject.meshOxidants - pharmacologyen_HK
dc.subject.meshOxidative Stress - drug effects - physiologyen_HK
dc.subject.meshPotassium Channel Blockers - pharmacologyen_HK
dc.subject.meshPotassium Channels - drug effects - metabolismen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.subject.meshTime Factorsen_HK
dc.titleMitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stressen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1161/01.STR.0000077017.60947.AEen_HK
dc.identifier.pmid12791941-
dc.identifier.scopuseid_2-s2.0-0038507050en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0038507050&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume34en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1796en_HK
dc.identifier.epage1802en_HK
dc.identifier.isiWOS:000183949200057-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTeshima, Y=7005407755en_HK
dc.identifier.scopusauthoridAkao, M=7005056367en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridChong, TH=36872202300en_HK
dc.identifier.scopusauthoridBaumgartner, WA=7203023284en_HK
dc.identifier.scopusauthoridJohnston, MV=7402060420en_HK
dc.identifier.scopusauthoridMarbán, E=8075977300en_HK

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