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Fish Stem Cells and Nuclear Transfer |
Int J Biol Sci 2007; 3:71-76 ©Ivyspring International Publisher Short Research Communication Role of TAB1 in nitric oxide-induced p38 activation in insulin-producing cells Department of Medical Cell Biology, Uppsala University, Sweden 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 How
to cite this article:
Makeeva N, Roomans GM, Welsh N. Role of TAB1 in nitric oxide-induced p38 activation in insulin-producing cells. Int J Biol Sci 2007; 3:71-76. Available from http://www.biolsci.org/v03p0071.htm |