Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells
(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.
(Less)
- author
- Jordán, Joaquín ; Galindo, María F ; Tornero, Daniel LU ; Benavides, Amparo ; González, Constancio ; Agapito, María T ; González-García, Carmen and Ceña, Valentín
- publishing date
- 2002-12
- 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
- Wiley
- external identifiers
-
- pmid:12429571
- 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
- 2024-01-04 01:18:22
@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}},
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}},
language = {{eng}},
number = {{7}},
pages = {{993--1000}},
publisher = {{Wiley}},
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}},
doi = {{10.1038/sj.bjp.0704953}},
volume = {{137}},
year = {{2002}},
}