Up-regulation of Bcl-2 by redox signals in glomerular mesangial cells.
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.
Sandau
K B
KB
Department of Medicine IV-Experimental Division, University of Erlangen-Nürnberg, Faculty of Medicine, 91054 Erlangen, Germany.
Brüne
B
B
D000818:Animals; D002478:Cells, Cultured; D003958:Diamide / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D003958:Diamide; D013481:Superoxides; D009569:Nitric Oxide; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase