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

J. Tejedo, Julio César Bernabé Ortíz, R. Ramírez, F. Sobrino, F. J. Bedoya

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)238-243
Number of pages6
JournalFEBS Letters
Volume459
Issue number2
DOIs
StatePublished - 8 Oct 1999
Externally publishedYes

Bibliographical note

Funding Information:
J.T.H. and J.C.B. were on leave of absence from the Universidad Nacional Jorge Basadre Grohmann, Tacna, Peru and from the Universidad Católica Santa Marı́a, Arequipa, Peru, respectively. This work was supported by grants from the Dirección General de Investigación Cientı́fica y Técnica (SAF 96/0205), Fondo de Investigaciones Sanitarias (97/1289) and Junta de Andalucı́a (200/98).

Keywords

  • Apoptosis
  • Caspase 3
  • Cyclic GMP
  • Cytochrome c
  • Nitric oxide
  • Pancreatic β-cell

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