Suppression of apoptosis by UVB irradiation: Survival signaling via P13-kinase/Akt pathway

UVB irradiation induces apoptosis in several cell types. However, me report here that UVB irradiation prevents induction of apoptosis in cells detache d from the extracellular matrix under serum-free conditions. NIH3T3 cells c ultured in bovine serum albumin-coated dishes (detached from the extracellu lar matrix) underwent apoptosis under serum-free conditions, which was inhi bited by UVB (<0.1 J/cm(2)) irradiation, keeping suspension conditions, as determined by chromatin condensation and the appearance of a subG1 DNA frac tion. Furthermore, UVB irradiation decreased caspase-3/7, -8/6, and -9 acti vation 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-mediat ed inhibition of cell death and recovered the inhibited caspase-3/7 activit y. Phosphorylation of Akt was observed from 15 min after UVB irradiation. T hese results suggested that UVB irradiation transduced a survival signal vi a PI3 kinase activation and phosphorylation of Akt, and induced some apopto sis inhibition factors upstream of the caspase cascade. (C) 2000 Academic P ress.