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NO induces a cGMP‐independent release of cytochrome c from mitochondria which precedes caspase 3 activation in insulin producing RINm5F cells
Author(s) -
Tejedo J,
Bernabé J.C,
Ramı́rez R,
Sobrino F,
Bedoya F.J
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01255-7
Subject(s) - sodium nitroprusside , cytochrome c , cgmp dependent protein kinase , apoptosis , mitochondrion , microbiology and biotechnology , caspase , chemistry , caspase 3 , downregulation and upregulation , protein kinase a , kinase , nitric oxide , programmed cell death , biology , biochemistry , endocrinology , mitogen activated protein kinase kinase , gene
Exposure of RINm5F cells to interleukin‐1β and to several chemical NO donors such as sodium nitroprusside (SNP), SIN‐1 and SNAP induce apoptotic events such as the release of cytochrome c from mitochondria, caspase 3 activation, Bcl‐2 downregulation and DNA fragmentation. SNP exposure led to transient activation of soluble guanylate cyclase (sGC) and prolonged protein kinase G (PKG) activation but apoptotic events were not attenuated by inhibition of the sGC/PKG pathway. Prolonged activation of the cGMP pathway by exposing cells to the dibutyryl analogue of cGMP for 12 h induced both apoptosis and necrosis, a response that was abolished by the PKG inhibitor KT5823. These results suggest that NO‐induced apoptosis in the pancreatic β‐cell line is independent of acute activation of the cGMP pathway.