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Superoxide anions mediate veratridine‐induced cytochrome c release and caspase activity in bovine chromaffin cells
Author(s) -
Jordán Joaquín,
Galindo María F,
Tornero Daniel,
Benavides Amparo,
González Constancio,
Agapito María T,
GonzálezGarcia Carmen,
Ceña Valentín
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704953
Subject(s) - veratridine , mitochondrial permeability transition pore , ruthenium red , superoxide , chemistry , cytochrome c , glutathione , chromaffin cell , mitochondrion , biochemistry , superoxide dismutase , programmed cell death , microbiology and biotechnology , biophysics , biology , endocrinology , oxidative stress , apoptosis , calcium , adrenal medulla , sodium , enzyme , organic chemistry , sodium channel , catecholamine
Mitochondrial mechanisms involved in veratridine‐induced chromaffin cell death have been explored. Exposure to veratridine (30 μ M , 1 h) produces cytochrome c release to the cytoplasm that seems to be mediated by superoxide anions and that is blocked by cyclosporin A (10 μ M ), MnTBAP (10 n M ), catalase (100 IU ml −1 ) and vitamin E (50 μ M ). Following veratridine treatment, there is an increase in caspase‐like activity, blocked by vitamin E (50 μ M ) and the mitochondrial permeability transition pore blocker cyclosporin A (10 μ M ). Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 μ M ) and cyclosporin A (10 μ M ), but not by the Ca 2+ uniporter blocker ruthenium red (5 μ M ). These results strongly suggest that under the stress situation caused by veratridine, superoxide anions become important regulators of mitochondrial function in chromaffin cells. Exposure of isolated bovine chromaffin mitochondria to Ca 2+ results in mitochondrial swelling. This effect was prevented by ruthenium red (5 μ M ) and cyclosporin A (10 μ M ), while it was not modified by vitamin E (50 μ M ). Veratridine (30 μ M , 1 h) markedly decreased total glutathione and GSH content in bovine chromaffin cells. In conclusion, superoxide anions seem to mediate veratridine‐induced cytochrome c release, decrease in total glutathione, caspase activation and cell death in bovine chromaffin cells.British Journal of Pharmacology (2002) 137 , 993–1000. doi: 10.1038/sj.bjp.0704953