Osmotic stress sensitizes naturally resistant cells to TNF-a induced apoptosis

FRANCO D L; NOJEK, I.; MOLINERO L,; COSO O. A.; MONICA ALEJANDRA COSTAS

Cell death and differentiation

Año: 2002 vol. 9 p. 1090 - 1098

1350-9047

Most cells are naturally resistant to TNF-a-induced cell death and become sensitized when NF-kB transactivation is blocked or in the presence of protein synthesis inhibitors that prevent the expression of anti-apoptotic genes. In this report we analyzed the role of osmotic stress on TNF-a-induced cell death. We found that it sensitizes the naturally resistant HeLa cells to TNF-a-induced apoptosis, with the involvement of an increase in the activity of several kinases, the inhibition of Bcl-2 expression, and a late increase on NF-kB activation. Cell death occurs regardless of the enhancedNF-kBactivity, whose inhibition produces an increase in apoptosis. The inhibition of p38 kinase, also involved in NF-kB activation, significantly increases the effect of osmotic stress on TNF-a-induced cell death.