Elevation of resting mitochondrial membrane potential of neural cells by cyclosporin A, BAPTA-AM, and Bcl-2
1 Department of Anesthesiology, The University of Maryland Baltimore, Baltimore, Maryland 21201; 2 Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil; 3 Section on Neuronal Secretory Systems, National Institute of Child Health...
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Published in | American Journal of Physiology: Cell Physiology Vol. 279; no. 3; pp. C852 - C859 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.09.2000
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Anesthesiology, The University of Maryland
Baltimore, Baltimore, Maryland 21201; 2 Departamento de
Patologia Clínica, Faculdade de Ciências Médicas,
Universidade Estadual de Campinas, Campinas, SP, Brazil;
3 Section on Neuronal Secretory Systems, National Institute of
Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland 20892; and 4 Departamento de
Farmacologia, Universidade Federal de São Paulo, UNIFESP,
São Paulo, Brazil
This study tested
the hypothesis that the activity of the mitochondrial membrane
permeability transition pore (PTP) affects the resting mitochondrial
membrane potential ( ) of normal, healthy cells and that the
anti-apoptotic gene product Bcl-2 inhibits the basal activity of the
PTP. 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 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 Ca 2+ chelation through exposure to the
acetoxymethyl ester of
1,2-bis(2-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid
(BAPTA-AM). The of Bcl-2-overexpressing PC12 cells was larger
than that of Bcl-2-negative cells and not significantly increased by
CsA or by Ca 2+ chelation. CsA did not present a significant
effect on the monitored in unstressed GT1-7 cells but did
inhibit the decrease in 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 of some cells and that Bcl-2 can regulate the
endogenous activity of the mitochondrial PTP.
calcium; mitochondrial permeability transition; energy metabolism
*
A. J. Kowaltowski and S. S. Smaili contributed
equally to this work. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.2000.279.3.C852 |