Suppression of apoptosis by UVB irradiation: survival signaling via PI3-kinase/Akt pathway

Biochem Biophys Res Commun. 2000 Dec 29;279(3):872-8. doi: 10.1006/bbrc.2000.4018.

Abstract

UVB irradiation induces apoptosis in several cell types. However, we report here that UVB irradiation prevents induction of apoptosis in cells detached from the extracellular matrix under serum-free conditions. NIH3T3 cells cultured in bovine serum albumin-coated dishes (detached from the extracellular matrix) underwent apoptosis under serum-free conditions, which was inhibited by UVB (<0.1 J/cm(2)) irradiation, keeping suspension conditions, as determined by chromatin condensation and the appearance of a subG1 DNA fraction. Furthermore, UVB irradiation decreased caspase-3/7, -8/6, and -9 activation and eliminated loss of mitochondrial inner transmembrane potential, suggesting suppression upstream of the caspase cascade. Treatment with PI3-kinase inhibitors, wortmannin, and LY294002 partly eliminated the UV-mediated inhibition of cell death and recovered the inhibited caspase-3/7 activity. Phosphorylation of Akt was observed from 15 min after UVB irradiation. These results suggested that UVB irradiation transduced a survival signal via PI3 kinase activation and phosphorylation of Akt, and induced some apoptosis inhibition factors upstream of the caspase cascade.

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis / radiation effects*
  • Caspases / physiology
  • Mice
  • Mitochondria / physiology
  • Mitochondria / radiation effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphorylation
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Ultraviolet Rays*

Substances

  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspases