Overxpression of Bcl-2 inhibits UVA-mediated immediate apoptosiinrat 6 fibroblasts: evidence for the involvement of Bcl-2 as an antioxidant.
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.
Pourzand
C
C
School of Pharmacy and Pharmacology, University of Bath, United Kingdo
Rossier
G
G
Reelfs
O
O
Borner
C
C
Tyrrell
R M
RM
D000818:Animals; D000975:Antioxidants; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D015152:Blotting, Northern; D053938:DNA Fragmentation; D004790:Enzyme Induction / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects*; D019254:Genes, bcl-2; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011933:Reagent Kits, Diagnostic; D013997:Time Factors; D014466:Ultraviolet Rays
D000975:Antioxidants; D012333:RNA, Messenger; D011933:Reagent Kits, Diagnostic; D006419:Heme Oxygenase (Decyclizing)