Keratinocyte apoptosis induced by ultraviolet B radiation and CD95 ligation -- differential protection through epidermal growth factor receptor activation and Bcl-x(L) expression.
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.
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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