title: Osmotic stress sensitizes naturally resistant cells to TNF-alpha-induced apoptosis.
abstract: 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.
authors.affiliation: 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.
authors.forename: D L
authors.initials: DL
authors.lastname: Franco
authors.forename: I M
authors.initials: IM
authors.lastname: Nojek
authors.forename: L
authors.initials: L
authors.lastname: Molinero
authors.forename: O A
authors.initials: OA
authors.lastname: Coso
authors.forename: M A
authors.initials: MA
authors.lastname: Costas
mesh_terms: 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
chemical_list: 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