Abstract

Keywords

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

KB Sandau & B Brüne

Correspondence to: B Brüne, University of Erlangen Nürnberg, Faculty of Medicine, Loschgestrasse 8, 91054 Erlangen, Germany. Tel: +49-9131-8536311; Fax: +49-9131-8539202; E-mail: mfm423@rzmail.uni-erlangen.de

Edited by J Stamler

The mediators nitric oxide (NO) and superoxide (O₂^–) are known to regulate cell death and survival. In mesangial cells (MC), NO induced apoptosis and in higher concentrations necrosis. Intriguingly, cogeneration of NO and O₂^– in a balanced ratio promoted cell protection. Under these conditions, we noticed the accumulation of the anti-apoptotic protein Bcl-2. Its up-regulation is based on an increase in mRNA and protein level. To investigate whether oxidative stress elicits Bcl-2 expression in general, we further used the chemically unrelated oxidative agents diamide and butyl hydroperoxide. Both stimulated mRNA and protein up-regulation 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 activator to protect MC against a subsequent toxic dose of NO. We conclude that redox changes promote Bcl-2 up-regulation that may confer cellular protection towards apoptosis. Cell Death and Differentiation (2000) 7, 118 – 125.

^© Macmillan Publishers Ltd 2000