Up-regulation of Bcl-2 by redox signals in glomerular mesangial cells

The mediators nitric oxide (NO) and superoxide (O-2(-)) are known to regula te cell death and survival, In mesangial cells (MC), NO induced apoptosis a nd in higher concentrations necrosis, Intriguingly, cogeneration of NO and O-2(-) in a balanced ratio promoted cell protection. Under these conditions , we noticed the accumulation of the anti-apoptotic protein Bcl-2. Its up-r egulation is based on an increase in mRNA and protein level. To investigate whether oxidative stress elicits Bcl-2 expression in general, we further u sed the chemically unrelated oxidative agents diamide and butyl hydroperoxi de, Both stimulated mRNA and protein upregulation of Bcl-2, But in contrast to diamide, butyl hydroperoxide evoked apoptosis and necrosis despite Bcl- 2 accumulation. As diamide was non-toxic, we used diamide as a Bcl-2 activa tor to protect MC against a subsequent toxic dose of NO. We conclude that r edox changes promote Bcl-2 upregulation that may confer cellular protection towards apoptosis.