Veratridine induces apoptotic death in bovine chromaffin cells through superoxide production.

Abstract:

:The molecular mechanisms involved in veratridine-induced chromaffin cell death have been explored. We have found that exposure to veratridine (30 microM, 1 h) produces a delayed cellular death that reaches 55% of the cells 24 h after veratridine exposure. This death has the features of apoptosis as DNA fragmentation can be observed. Calcium ions play an important role in veratridine-induced chromaffin cell death because the cell permeant Ca(2+) chelator BAPTA-AM and extracellular Ca(2+) removal completely prevented veratridine-induced toxicity. Following veratridine treatment, there is a decrease in mitochondrial function and an increase in superoxide anion production. Veratridine-induced increase in superoxide production was blocked by tetrodotoxin (TTX; 10 microM), extracellular Ca(2+) removal and the mitochondrial permeability transition pore blocker cyclosporine A (10 microM). Veratridine-induced death was prevented by different antioxidant treatments including catalase (100 IU ml(-1)), N-acetyl cysteine (100 microM), allopurinol (100 microM) or vitamin E (50 microM). Veratridine-induced DNA fragmentation was prevented by TTX (10 microM). Veratridine produced a time-dependent increase in caspase activity that was prevented by Ca(2+) removal and TTX (10 microM). In addition, calpain and caspases inhibitors partially prevented veratridine-induced death. These results indicate that chromaffin cells share with neurons the molecular machinery involved in apoptotic death and might be considered a good model to study neuronal death during neurodegeneration.

journal_name

Br J Pharmacol

authors

Jordán J,Galindo MF,Calvo S,González-García C,Ceña V

doi

10.1038/sj.bjp.0703451

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

1496-504

issue

7

eissn

0007-1188

issn

1476-5381

journal_volume

130

pub_type

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