title: Cytokine and low-level nitric oxide prestimulation block p53 accumulation and apoptosis of RAW 264.7 macrophages.
abstract: Nitric oxide causes apoptotic cell death in RAW 264.7 macrophages. The cellular response to the NO donor S-nitrosoglutathione (GSNO) comprises an apoptotic morphology and DNA fragmentation, which largely depends on the accumulation of the tumor suppressor gene product p53. Pre-treatment of macrophages with LPS, IFN-gamma in the presence of NG-monomethyl-L-arginine (NMMA) imparts resistance to apoptotic cell death, normally elicited by exogenously-supplied GSNO. Similarly, pre-treatment with low-dose GSNO (25-200 microM) conferred resistance from a second exposure to a higher dose of GSNO (1 mM). Protection is comprehended at the level of blocked p53 accumulation. Upregulation of protective mechanisms in response to non-lethal NO concentrations or by LPS, cytokine pre-stimulation may redirect the ability of nitric oxide to upregulate p53 and to initiate macrophage apoptosis, thereby modulating cellular susceptibility towards NO-intoxication.
authors.affiliation: Faculty of Medicine, Department of Medicine IV-Experimental Division, University of Erlangen-Nürnberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Brüne
authors.forename: C
authors.initials: C
authors.lastname: Gölkel
authors.forename: A
authors.initials: A
authors.lastname: von Knethen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide