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Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells

Jordán, Joaquín; Galindo, María F; Tornero, Daniel LU ; Benavides, Amparo; González, Constancio; Agapito, María T; González-García, Carmen and Ceña, Valentín (2002) In British Journal of Pharmacology 137(7). p.993-1000
Abstract

1. Mitochondrial mechanisms involved in veratridine-induced chromaffin cell death have been explored. 2. Exposure to veratridine (30 micro 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 micro M), MnTBAP (10 nM), catalase (100 IU ml(-1)) and vitamin E (50 micro M). 3. Following veratridine treatment, there is an increase in caspase-like activity, blocked by vitamin E (50 micro M) and the mitochondrial permeability transition pore blocker cyclosporin A (10 micro M). 4. Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 micro M) and cyclosporin A (10 micro... (More)

1. Mitochondrial mechanisms involved in veratridine-induced chromaffin cell death have been explored. 2. Exposure to veratridine (30 micro 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 micro M), MnTBAP (10 nM), catalase (100 IU ml(-1)) and vitamin E (50 micro M). 3. Following veratridine treatment, there is an increase in caspase-like activity, blocked by vitamin E (50 micro M) and the mitochondrial permeability transition pore blocker cyclosporin A (10 micro M). 4. Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 micro M) and cyclosporin A (10 micro M), but not by the Ca2+ uniporter blocker ruthenium red (5 micro M). 5. These results strongly suggest that under the stress situation caused by veratridine, superoxide anions become important regulators of mitochondrial function in chromaffin cells. 6. Exposure of isolated bovine chromaffin mitochondria to Ca2+ results in mitochondrial swelling. This effect was prevented by ruthenium red (5 micro M) and cyclosporin A (10 micro M), while it was not modified by vitamin E (50 micro M). 7. Veratridine (30 micro M, 1 h) markedly decreased total glutathione and GSH content in bovine chromaffin cells. 8. 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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Acetylcysteine, Animals, Buthionine Sulfoximine, Calcium, Caspases, Catalase, Cattle, Cell Survival, Chromaffin Cells, Cyclosporine, Cytochrome c Group, Enzyme Activation, Glutathione, Metalloporphyrins, Mitochondria, Permeability, Superoxides, Veratridine, Vitamin E
in
British Journal of Pharmacology
volume
137
issue
7
pages
8 pages
publisher
The British Pharmacological Society
external identifiers
  • scopus:0036900713
ISSN
0007-1188
DOI
10.1038/sj.bjp.0704953
language
English
LU publication?
no
id
dc3b2210-5bf0-4f82-a56a-b7e3b5a91432
date added to LUP
2016-04-11 15:23:54
date last changed
2017-01-01 08:22:31
@article{dc3b2210-5bf0-4f82-a56a-b7e3b5a91432,
  abstract     = {<p>1. Mitochondrial mechanisms involved in veratridine-induced chromaffin cell death have been explored. 2. Exposure to veratridine (30 micro 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 micro M), MnTBAP (10 nM), catalase (100 IU ml(-1)) and vitamin E (50 micro M). 3. Following veratridine treatment, there is an increase in caspase-like activity, blocked by vitamin E (50 micro M) and the mitochondrial permeability transition pore blocker cyclosporin A (10 micro M). 4. Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 micro M) and cyclosporin A (10 micro M), but not by the Ca2+ uniporter blocker ruthenium red (5 micro M). 5. These results strongly suggest that under the stress situation caused by veratridine, superoxide anions become important regulators of mitochondrial function in chromaffin cells. 6. Exposure of isolated bovine chromaffin mitochondria to Ca2+ results in mitochondrial swelling. This effect was prevented by ruthenium red (5 micro M) and cyclosporin A (10 micro M), while it was not modified by vitamin E (50 micro M). 7. Veratridine (30 micro M, 1 h) markedly decreased total glutathione and GSH content in bovine chromaffin cells. 8. 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.</p>},
  author       = {Jordán, Joaquín and Galindo, María F and Tornero, Daniel and Benavides, Amparo and González, Constancio and Agapito, María T and González-García, Carmen and Ceña, Valentín},
  issn         = {0007-1188},
  keyword      = {Acetylcysteine,Animals,Buthionine Sulfoximine,Calcium,Caspases,Catalase,Cattle,Cell Survival,Chromaffin Cells,Cyclosporine,Cytochrome c Group,Enzyme Activation,Glutathione,Metalloporphyrins,Mitochondria,Permeability,Superoxides,Veratridine,Vitamin E},
  language     = {eng},
  number       = {7},
  pages        = {993--1000},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0704953},
  volume       = {137},
  year         = {2002},
}