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-1beta 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 beta-cell line is independent of acute activation of the cGMP pathway.
Tejedo
J
J
Laboratory of Biochemistry of the Immune System, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, University of Sevilla, Avenida Dr. Fedriani s/n, 41018, Sevilla, Spain.
Bernabé
J C
JC
Ramírez
R
R
Sobrino
F
F
Bedoya
F J
FJ
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases; D003574:Cytochrome c Group / Q000378:metabolism*; D004249:DNA Damage; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D003574:Cytochrome c Group; D007328:Insulin; D019253:Proto-Oncogene Proteins c-bcl-2; D009599:Nitroprusside; D009569:Nitric Oxide; D011494:Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D006162:Guanylate Cyclase; D006152:Cyclic GMP