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

The relationship between oxidative stress and Bcl-2 expression was investigated in two different experimental models of oxidative stress. Acute oxidative stress was assessed by measuring, with fluorescence microscopy and cytofluorimetry, 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 significant increase in the level of nucleosomes. Interestingly, chronic treatment with clinical concentrations of cyclosporin A (0.5-2.5 mu M for 8 days) led to a significant increase in Bcl-2 expression, while nucleosomes were similar to control level. This suggests that up-regulation of Bcl-2 protein by low levels of oxidants may represent a critical factor in cellular adaptation to drug toxicity. (C) 1999 Academic Press.