Elevation of resting mitochondrial membrane potential of neural cells by cyclosporin A, BAPTA-AM, and Bcl-2

Elevation of resting mitochondrial membrane potential of neural cells by cyclosporin A, BAPTA-AM, and Bcl-2

Author Kowaltowski, Alicia J. Google Scholar
Smaili, Soraya Soubhi Autor UNIFESP Google Scholar
Russell, James T. Google Scholar
Fiskum, Gary Google Scholar
Institution Univ Maryland
Universidade Estadual de Campinas (UNICAMP)
NICHHD
Universidade Federal de São Paulo (UNIFESP)
Abstract This study tested the hypothesis that the activity of the mitochondrial membrane permeability transition pore (PTP) affects the resting mitochondrial membrane potential (Delta Psi) of normal, healthy cells and that the anti-apoptotic gene product Bcl-2 inhibits the basal activity of the PTP. Delta Psi was measured by both fluorometric and nonfluorometric methods with SY5Y human neuroblastoma cells and with GT1-7 hypothalamic cells and PC12 pheochromocytoma cells in the absence and presence of Bcl-2 gene overexpression. The resting Delta Psi of Bcl-2 nonexpressing PC12 and wild-type SY5Y cells was increased significantly by the presence of the PTP inhibitor cyclosporin A (CsA) or by intracellular Ca2+ chelation through exposure to the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). The Delta Psi of Bcl-2-overexpressing PC12 cells was larger than that of Bcl-2-negative cells and not significantly increased by CsA or by Ca2+ chelation. CsA did not present a significant effect on the Delta Psi monitored in unstressed GT1-7 cells but did inhibit the decrease in Delta Psi elicited by the addition of t-butyl hydroperoxide, an oxidative inducer of the mitochondrial permeability transition. These results support the hypothesis that an endogenous PTP activity can contribute to lowering the basal Delta Psi of some cells and that Bcl-2 can regulate the endogenous activity of the mitochondrial PTP.
Keywords calcium
mitochondrial permeability transition
energy metabolism
Language English
Date 2000-09-01
Published in American Journal Of Physiology-cell Physiology. Bethesda: Amer Physiological Soc, v. 279, n. 3, p. C852-C859, 2000.
ISSN 0363-6143 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent C852-C859
Origin http://ajpcell.physiology.org/content/279/3/C852
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000088745000030
URI http://repositorio.unifesp.br/11600/42346

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