Mitochondrial Permeability Transition In Neuronal Damage Promoted By Ca2+ And Respiratory Chain Complex Ii Inhibition.

dc.creatorMaciel, Evelise N
dc.creatorKowaltowski, Alicia J
dc.creatorSchwalm, Fábio D
dc.creatorRodrigues, Juliana M
dc.creatorSouza, Diogo O
dc.creatorVercesi, Anibal E
dc.creatorWajner, Moacir
dc.creatorCastilho, Roger F
dc.date2004-Sep
dc.date2015-11-27T12:58:23Z
dc.date2015-11-27T12:58:23Z
dc.date.accessioned2018-03-29T00:59:29Z
dc.date.available2018-03-29T00:59:29Z
dc.identifierJournal Of Neurochemistry. v. 90, n. 5, p. 1025-35, 2004-Sep.
dc.identifier0022-3042
dc.identifier10.1111/j.1471-4159.2004.02565.x
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/15312158
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/195919
dc.identifier15312158
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1296152
dc.descriptionChanges in mitochondrial integrity, reactive oxygen species release and Ca2+ handling are proposed to be involved in the pathogenesis of many neurological disorders including methylmalonic acidaemia and Huntington's disease, which exhibit partial mitochondrial respiratory inhibition. In this report, we studied the mechanisms by which the respiratory chain complex II inhibitors malonate, methylmalonate and 3-nitropropionate affect rat brain mitochondrial function and neuronal survival. All three compounds, at concentrations which inhibit respiration by 50%, induced mitochondrial inner membrane permeabilization when in the presence of micromolar Ca2+ concentrations. ADP, cyclosporin A and catalase prevented or delayed this effect, indicating it is mediated by reactive oxygen species and mitochondrial permeability transition (PT). PT induced by malonate was also present in mitochondria isolated from liver and kidney, but required more significant respiratory inhibition. In brain, PT promoted by complex II inhibition was stimulated by increasing Ca2+ cycling and absent when mitochondria were pre-loaded with Ca2+ or when Ca2+ uptake was prevented. In addition to isolated mitochondria, we determined the effect of methylmalonate on cultured PC12 cells and freshly prepared rat brain slices. Methylmalonate promoted cell death in striatal slices and PC12 cells, in a manner attenuated by cyclosporin A and bongkrekate, and unrelated to impairment of energy metabolism. We propose that under conditions in which mitochondrial complex II is partially inhibited in the CNS, neuronal cell death involves the induction of PT.
dc.description90
dc.description1025-35
dc.languageeng
dc.relationJournal Of Neurochemistry
dc.relationJ. Neurochem.
dc.rightsfechado
dc.rightsCopyright 2004 International Society for Neurochemistry
dc.sourcePubMed
dc.subjectAnimals
dc.subjectAntimycin A
dc.subjectBongkrekic Acid
dc.subjectBrain
dc.subjectCalcimycin
dc.subjectCalcium
dc.subjectCatalase
dc.subjectCell Survival
dc.subjectCyclosporins
dc.subjectDose-response Relationship, Drug
dc.subjectDrug Interactions
dc.subjectElectron Transport Complex Ii
dc.subjectEnzyme Inhibitors
dc.subjectFemale
dc.subjectIn Vitro Techniques
dc.subjectIonophores
dc.subjectMalonates
dc.subjectMembrane Potentials
dc.subjectMethylmalonic Acid
dc.subjectMitochondria
dc.subjectNadp
dc.subjectNeurons
dc.subjectNitro Compounds
dc.subjectOxygen Consumption
dc.subjectPc12 Cells
dc.subjectPermeability
dc.subjectPropionates
dc.subjectRats
dc.subjectRotenone
dc.subjectTacrolimus
dc.subjectTetrazolium Salts
dc.subjectThiazoles
dc.subjectUncoupling Agents
dc.titleMitochondrial Permeability Transition In Neuronal Damage Promoted By Ca2+ And Respiratory Chain Complex Ii Inhibition.
dc.typeArtículos de revistas


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