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Int J Biol Sci 2007; 3(2):71-76. doi:10.7150/ijbs.3.71 This issue Cite

Short Research Communication

Role of TAB1 in nitric oxide-induced p38 activation in insulin-producing cells

Natalia Makeeva, Godfried M. Roomans, Nils Welsh

Department of Medical Cell Biology, Uppsala University, Sweden

Abstract

The aim of present study was to elucidate the role of TAB1 in nitric oxide-induced activation of p38 MAPK. For this purpose we over-expressed TAB1 in insulin-producing β-TC6 cells. We observed in cells transiently over-expressing TAB1 that p38 activation was enhanced in response to DETA/NONOate. A lowering of TAB1 levels, using the siRNA technique, resulted in the opposite effect. The DETA/NONOate-induced cell death rate was increased in cells transiently overexpressing TAB1. In stable β-TC6 cell clones with very high TAB1 levels p38 phosphorylation was enhanced also at basal conditions. DETA/NONOate increased also the phosphorylation of JNK and ERK in β-TC6 cells, but these events were not affected by TAB1. Interestingly, the inhibitory effect of SB203580 on p38 phosphorylation was paralleled by a stimulatory effect on JNK phosphorylation and an inhibitory effect on ERK phosphorylation. In summary, we propose that TAB1 promotes nitric oxide-induced p38 autophosphorylation. In addition, nitric oxide-induced p38 activation seems to promote JNK inhibition and ERK activation, but this effect appears to not require TAB1. A better understanding of how the TAB1/p38 pathway promotes β-cell death in response to nitric oxide might help in the development of novel pharmacological approaches in the treatment of diabetes.

Keywords: apoptosis, nitric oxide, insulin producing cell, TAB1, p38 MAPK

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