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

DL FRANCO, IM NOJEK, L MOLINERO, OA COSO AND MA COSTAS

CELL DEATH AND DIFFERENTIATION

Nature Publishing group

Lugar: United Kingdom; Año: 2002 p. 1090 - 1098

1350-9047

Most cells are naturally resistant to TNF--induced cell death and become sensitized when NF-B 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--induced cell death. We found that it sensitizes the naturally resistant HeLa cells to TNF--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-B activation. Cell death occurs regardless of the enhanced NF-B activity, whose inhibition produces an increase in apoptosis. The inhibition of p38 kinase, also involved in NF-B activation, significantly increases the effect of osmotic stress on TNF--induced cell death.