Regulation of Bcl-2 protein expression during oxidative stress in neuronaland in endothelial cells

The relationship between oxidative stress and Bcl-2 expression was investig ated in two different experimental models of oxidative stress. Acute oxidat ive stress was assessed by measuring, with fluorescence microscopy and cyto fluorimetry, the increase in fluorescence of the oxidation-sensitive probe dihydrorhodamine 123, both in retinal rod receptor cells exposed to bright light (0.32 mW/cm(2) for 15 minutes) and in human endothelial cells treated with the immunosuppressant cyclosporin A (200 mu M for 21 h). In both cell types, acute oxidative stress reduced Bcl-2 expression and also caused a s ignificant increase in the level of nucleosomes. Interestingly, chronic tre atment with clinical concentrations of cyclosporin A (0.5-2.5 mu M for 8 da ys) led to a significant increase in Bcl-2 expression, while nucleosomes we re similar to control level. This suggests that up-regulation of Bcl-2 prot ein by low levels of oxidants may represent a critical factor in cellular a daptation to drug toxicity. (C) 1999 Academic Press.