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Keratinocyte apoptosis induced by ultraviolet B radiation and CD95 ligation -- differential protection through epidermal growth factor receptor activation and Bcl-x(L) expression.
Jost, M; Gasparro, F P; Jensen, P J; Rodeck, U.
Afiliação
  • Jost M; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, and Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
J Invest Dermatol ; 116(6): 860-6, 2001 Jun.
Article em En | MEDLINE | ID: mdl-11407972
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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteção Radiológica / Raios Ultravioleta / Queratinócitos / Apoptose / Receptor fas / Proteínas Proto-Oncogênicas c-bcl-2 / Receptores ErbB Limite: Humans Idioma: En Revista: J Invest Dermatol Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteção Radiológica / Raios Ultravioleta / Queratinócitos / Apoptose / Receptor fas / Proteínas Proto-Oncogênicas c-bcl-2 / Receptores ErbB Limite: Humans Idioma: En Revista: J Invest Dermatol Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos