Alterations in cell death and cell cycle progression in the UV-irradiated epidermis of bcl-2-deficient mice.
The effect of bcl-2 gene ablation on epidermal cell death induced by UV-B irradiation was investigated in mice. Exposure of depilated back skin of bcl-2-/- mice to 0.5 J/cm2 UV-B caused a prolonged increase in the number of epidermal cells showing nuclear DNA fragmentation compared to wild-type littermates. Consistently, skin explants from bcl-2-deficient mice exhibited a higher number of sunburn cells per cm epidermis (16.6+/-2.1 vs 7.0+/-1.5) following exposure to 0.1 J/cm2 UV-B in vitro. Furthermore, UV irradiation failed to increase pre-melanosomes in skin explants from mutant animals, and primary menalocyte cultures derived from bcl-2 null mutants were highly susceptible to UV-induced cell death compared to cultures from wild-type littermates. An accelerated reappearance of proliferating cells, showing nuclear immunoreactivity for Ki-67 and c-Fos, was observed in the UV-irradiated epidermis of bcl-2-deficient mice. Taken together, these findings suggest that effects of UV radiation on epidermal cell death and cell cycle progression are influenced by survival-promoting Bcl-2.
Gillardon
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II. Physiologisches Institut, Universität Heidelberg, Heidelberg, Germany. gillardo@ing.boehringer-ingelheim.com
Moll
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Meyer
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Michaelidis
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TM
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D002452:Cell Count / Q000528:radiation effects; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects*; D053938:DNA Fragmentation / Q000235:genetics / Q000528:radiation effects; D004817:Epidermis / Q000528:radiation effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008544:Melanocytes / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics*; D014466:Ultraviolet Rays
D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2