NO induces a cGMP-independent release of cytochrome c from mitochondria which precedes caspase 3 activation in insulin producing RINm5F cells

Exposure of RINm5F cells to interleukin-1 beta and to several chemical NO d onors such as sodium nitroprusside (SNP), SIN-1 and SNAP induce apoptotic e vents such as the release of cytochrome c from mitochondria, caspase 3 acti vation, Bcl-2 downregulation and DNA fragmentation. SNP exposure led to tra nsient activation of soluble guanylate cyclase (sGC) and prolonged protein kinase G (PKG) activation but apoptotic events were not attenuated by inhib ition of the sGC/PKG pathway, Prolonged activation of the cGMP pathway by e xposing cells to the dibutyryl analogue of cGMP for 12 h induced both apopt osis and necrosis, a response that was abolished by the PKG inhibitor KT582 3, These results suggest that NO-induced apoptosis in the pancreatic beta-c ell line is independent of acute activation of the cGMP pathway. (C) 1999 F ederation of European Biochemical Societies.