Osmotic stress sensitizes naturally resistant cells to TNF-alpha-induced apoptosis.
Most cells are naturally resistant to TNF-alpha-induced cell death and become sensitized when NF-kappaB 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-alpha-induced cell death. We found that it sensitizes the naturally resistant HeLa cells to TNF-alpha-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-kappaB activation. Cell death occurs regardless of the enhanced NF-kappaB activity, whose inhibition produces an increase in apoptosis. The inhibition of p38 kinase, also involved in NF-kappaB activation, significantly increases the effect of osmotic stress on TNF-alpha-induced cell death.
Franco
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DL
Laboratorio de Fisiología y Biología Molecular, Departamento de Cs. Biológicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA Bs. As., Argentina.
Nojek
I M
IM
Molinero
L
L
Coso
O A
OA
Costas
M A
MA
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D048291:Mitogen-Activated Protein Kinase 12; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012462:Saline Solution, Hypertonic; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D048291:Mitogen-Activated Protein Kinase 12; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases