Veratridine induces apoptotic death in bovine chromaffin cells through superoxide production

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Abstract
The molecular mechanisms involved in veratridine‐induced chromaffin cell death have been explored. We have found that exposure to veratridine (30 μM, 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 Ca2+ chelator BAPTA‐AM and extracellular Ca2+ 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 μM), extracellular Ca2+ removal and the mitochondrial permeability transition pore blocker cyclosporine A (10 μM). Veratridine‐induced death was prevented by different antioxidant treatments including catalase (100 IU ml−1), N‐acetyl cysteine (100 μM), allopurinol (100 μM) or vitamin E (50 μM). Veratridine‐induced DNA fragmentation was prevented by TTX (10 μM). Veratridine produced a time‐dependent increase in caspase activity that was prevented by Ca2+ removal and TTX (10 μM). 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. British Journal of Pharmacology (2000) 130, 1496–1504; doi:10.1038/sj.bjp.0703451