Tissue And Sex Specificities In Ca2+ Handling By Isolated Mitochondria In Conditions Avoiding The Permeability Transition

dc.creatorChweih
dc.creatorHanan; Castilho
dc.creatorRoger F.; Figueira
dc.creatorTiago R.
dc.date2015-SEP
dc.date2016-06-07T13:21:15Z
dc.date2016-06-07T13:21:15Z
dc.date.accessioned2018-03-29T01:41:08Z
dc.date.available2018-03-29T01:41:08Z
dc.identifier
dc.identifierTissue And Sex Specificities In Ca2+ Handling By Isolated Mitochondria In Conditions Avoiding The Permeability Transition. Wiley-blackwell, v. 100, p. 1073-1092 SEP-2015.
dc.identifier0958-0670
dc.identifierWOS:000360625800011
dc.identifier10.1113/EP085248
dc.identifierhttp://onlinelibrary.wiley.com/doi/10.1113/EP085248/full
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/243054
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1306752
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionNew Findings What is the central question of this study? The assessment of Ca2+ handling by isolated mitochondria can be biased by dysfunctions secondary to Ca2+-induced mitochondrial permeability transition (MPT). As a result of this uncertainty and the differing experimental conditions between studies, the tissue and sex diversities in mitochondrial Ca2+ transport are still unsettled questions. What is the main finding and its importance? If MPT is not prevented during Ca2+ transport assays, some measured variables are biased. Accounting for the implied importance of preventing MPT, we observed substantial tissue specificities in the mitochondrial Ca2+ handling, particularly in the Ca2+ efflux pathways. The characteristics of mitochondria, including their Ca2+ transport functions, may exhibit tissue specificity and sexual dimorphism. Given that measurements of Ca2+ handling by isolated mitochondria may be biased by dysfunction secondary to Ca2+-induced mitochondrial permeability transition (MPT) pore opening, this study evaluated the extent to which MPT inhibition by ciclosporin affected the measurement of Ca2+ transport in isolated rat liver mitochondria. The results indicate that the steady-state levels of external Ca2+ and the rates of mitochondrial Ca2+ efflux through the selective pathways can be overestimated by up to fourfold if MPT pore opening is not prevented. We analysed Ca2+ transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats in incubation conditions containing MPT inhibitors, NAD-linked substrates and relevant levels of free Ca2+, Mg2+ and Na+. The Ca2+ influx rates were similar among the samples, except that the liver mitochondria displayed values fourfold higher. In contrast, the Ca2+ efflux rates exhibited more tissue diversity, especially in the presence of Na+. Interestingly, the Na+-independent Ca2+ efflux was highest in the heart mitochondria (approximate to 4nmolmg(-1)min(-1)), thus challenging the view that cardiac mitochondrial Ca2+ efflux relies almost exclusively on a Na+-dependent pathway. Sex specificity was observed in only two kinetic indexes of heart mitochondrial Ca2+ homeostasis and in the ADP-stimulated respiration of liver mitochondria (approximate to 20% higher in females). The present study shows the methodological importance of preventing MPT when measuring the properties and the physiological variability of the Ca2+ handling by isolated mitochondria.
dc.description100
dc.description9
dc.description
dc.description1073
dc.description1092
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFAPESP [11/50400-0]
dc.descriptionFAPESP [2011/51800-1]
dc.description
dc.description
dc.description
dc.languageen
dc.publisherWILEY-BLACKWELL
dc.publisher
dc.publisherHOBOKEN
dc.relationEXPERIMENTAL PHYSIOLOGY
dc.rightsfechado
dc.sourceWOS
dc.subjectRat-liver Mitochondria
dc.subjectCalcium Uniporter
dc.subjectHeart-mitochondria
dc.subjectCardiac Mitochondria
dc.subjectCaloric Restriction
dc.subjectEssential Component
dc.subjectReactive Oxygen
dc.subjectSodium
dc.subjectEfflux
dc.subjectTransport
dc.titleTissue And Sex Specificities In Ca2+ Handling By Isolated Mitochondria In Conditions Avoiding The Permeability Transition
dc.typeArtículos de revistas


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