Overxpression of Bcl-2 inhibits UVA-mediated immediate apoptosiinrat 6 fibroblasts: evidence for the involvement of Bcl-2 as an antioxidant

Cancer Res. 1997 Apr 15;57(8):1405-11.

Abstract

We examined the effect of broad spectrum UVA (320-380 nm) and UVB (290-320 nm) radiation on the induction of apoptosis in the rat 6 fibroblast cell line (R6). UVA, but not UVB, induces apoptosis in this cell line. The morphological changes and DNA ladders associated with apoptosis occurred within the first 4 h after UVA irradiation, a phenomenon referred to as "immediate" apoptosis. From previous studies, it is known that Bcl-2 inhibits most types of apoptotic cell death. Overexpression of mouse Bcl-2 in the R6 fibroblasts inhibited the UVA-induced immediate apoptosis. The induction of the heme oxygenase 1 (HO-1) gene by UVA is a general response to oxidative stress. As a marker of oxidative stress, we monitored the effect of Bcl-2 overexpression on the level of HO-1 mRNA accumulation after UVA irradiation. The results showed that the overexpression of Bcl-2 in the R6 fibroblasts strongly reduces the level of HO-1 induction from 12.5- to 4.9-fold. We propose that Bcl-2 expression inhibits UVA-induced immediate apoptosis via an antioxidant pathway, suppressing either the generation or effects of specific UVA-mediated reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants
  • Apoptosis / genetics
  • Apoptosis / radiation effects*
  • Blotting, Northern
  • DNA Fragmentation
  • Enzyme Induction / genetics
  • Enzyme Induction / radiation effects
  • Fibroblasts / radiation effects
  • Gene Expression / genetics
  • Gene Expression / radiation effects*
  • Genes, bcl-2*
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase (Decyclizing) / radiation effects*
  • Mice
  • Oxidative Stress
  • RNA, Messenger / metabolism
  • Rats
  • Reagent Kits, Diagnostic
  • Time Factors
  • Ultraviolet Rays

Substances

  • Antioxidants
  • RNA, Messenger
  • Reagent Kits, Diagnostic
  • Heme Oxygenase (Decyclizing)