Keratinocyte apoptosis induced by ultraviolet B radiation and CD95 ligation -- differential protection through epidermal growth factor receptor activation and Bcl-x(L) expression.
Previous work has shown that activation of the epidermal growth factor receptor by endogenous or exogenous signals markedly enhances survival of cultured keratinocytes upon cellular stress such as passaging. This is due, in part, to epidermal-growth-factor-receptor-dependent expression of Bcl-x(L), an antiapoptotic Bcl-2 homolog. In this study we tested whether epidermal-growth-factor-receptor-dependent signal transduction and attendant Bcl-x(L) expression affected survival of human keratinocytes upon exposure to a frequently encountered apoptotic stimulus, radiation with ultraviolet B. We describe that blocking epidermal-growth-factor-receptor-dependent signal transduction sensitized normal keratinocytes to undergo apoptosis upon ultraviolet B radiation with solar light characteristics. Forced expression of Bcl-x(L) partially but significantly inhibited ultraviolet-B-induced apoptosis of immortalized keratinocytes (HaCaT). Bcl-x(L) overexpression afforded no protection to HaCaT cells against apoptosis induced by binding of an agonist antibody to the death receptor CD95, however. CD95 activation has previously been shown to functionally contribute to apoptosis in ultraviolet-irradiated keratinocytes. These results indicate that epidermal growth factor receptor activation and attendant Bcl-x(L) expression provided a physiologically relevant protective pathway of keratinocytes against ultraviolet-induced but not CD95-dependent apoptosis.
Jost
M
M
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, and Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Gasparro
F P
FP
Jensen
P J
PJ
Rodeck
U
U
D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology / Q000528:radiation effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011835:Radiation Protection; D014466:Ultraviolet Rays; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology*
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; D066246:ErbB Receptors