Nitric oxide induces and inhibits apoptosis through different pathways

FEBS Lett. 1998 Aug 14;433(1-2):125-31. doi: 10.1016/s0014-5793(98)00844-8.


Physiological levels of nitric oxide (NO) regulate vascular tone and protect the microvasculature from injury whereas excessive NO may be harmful. The present study explored the effects of NO on human endothelial cell apoptosis. We found that the NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibited TNFalpha-induced endothelial apoptosis and that this was mediated partly through the cGMP pathway. In contrast, high SNAP concentration induced endothelial apoptosis via cGMP-independent pathways and the cGMP pathway protected against NO-induced apoptosis. These findings demonstrate that low NO concentrations contribute to human endothelial cell survival, whereas higher NO concentrations are pathological and promote destruction of endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / pharmacology
  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cyclic GMP / pharmacology
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Enzyme Inhibitors / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Humans
  • Nitric Oxide / pharmacology*
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins


  • Aminoquinolines
  • Enzyme Inhibitors
  • S-nitro-N-acetylpenicillamine
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • 6-anilino-5,8-quinolinedione
  • Guanylate Cyclase
  • Penicillamine
  • Cyclic GMP