Statins Induce Calcium-dependent Mitochondrial Permeability Transition.

dc.creatorVelho, Jesus A
dc.creatorOkanobo, Heitor
dc.creatorDegasperi, Giovanna R
dc.creatorMatsumoto, Márcio Y
dc.creatorAlberici, Luciane C
dc.creatorCosso, Ricardo G
dc.creatorOliveira, Helena C F
dc.creatorVercesi, Anibal E
dc.date2006-Feb
dc.date2015-11-27T13:05:43Z
dc.date2015-11-27T13:05:43Z
dc.date.accessioned2018-03-29T01:03:17Z
dc.date.available2018-03-29T01:03:17Z
dc.identifierToxicology. v. 219, n. 1-3, p. 124-32, 2006-Feb.
dc.identifier0300-483X
dc.identifier10.1016/j.tox.2005.11.007
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/16343726
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/196894
dc.identifier16343726
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1297127
dc.descriptionStatins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are used in the treatment of hypercholesterolemic patients to reduce risk of cardiovascular diseases because of their cholesterol lowering action. Other lipid independent protective actions of statins have been reported. However, some adverse side effects have, also, been described. We report, here, that liver mitochondria isolated from hypercholesterolemic LDL receptor knockout mice treated during 15 days with therapeutic doses (100 mg/kg, p.o.) of lovastatin presented a higher susceptibility to develop membrane permeability transition (MPT). In experiments in vitro, lovastatin-induced MPT in a dose-dependent manner (10-80 microM) by a mechanism sensitive to cyclosporin A (cyclophilin sequestrant), dithiothreitol (reducing agent), adenine nucleotide carrier inhibitor (ADP), catalase (H2O2 reductant) and EGTA (calcium chelator). In agreement with the inhibition of the mitochondrial swelling by dithiothreitol, lovastatin, also, decreased the content of total mitochondrial membrane protein thiol groups. Simvastatin had similar effects on mitochondria; however, pravastatin, a hydrophilic statin, had a weaker effect in inducing MPT. In conclusion, statins can act directly on mitochondria either in vivo or in vitro inducing permeability transition, which is a process involved in cell death.
dc.description219
dc.description124-32
dc.languageeng
dc.relationToxicology
dc.relationToxicology
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAdenosine Diphosphate
dc.subjectAnimals
dc.subjectCatalase
dc.subjectChelating Agents
dc.subjectCholesterol
dc.subjectDithiothreitol
dc.subjectEgtazic Acid
dc.subjectElectrophysiology
dc.subjectHindlimb
dc.subjectHydroxymethylglutaryl-coa Reductase Inhibitors
dc.subjectIn Vitro Techniques
dc.subjectLovastatin
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMitochondria, Liver
dc.subjectMitochondria, Muscle
dc.subjectMitochondrial Swelling
dc.subjectPermeability
dc.subjectPhenazines
dc.subjectProteins
dc.subjectReceptors, Ldl
dc.subjectSulfhydryl Compounds
dc.subjectSulfhydryl Reagents
dc.titleStatins Induce Calcium-dependent Mitochondrial Permeability Transition.
dc.typeArtículos de revistas


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