Brüne B, Gölkel C, von Knethen A
Faculty of Medicine, Department of Medicine IV-Experimental Division, University of Erlangen-Nürnberg, Germany.
Biochem Biophys Res Commun. 1996 Dec 13;229(2):396-401. doi: 10.1006/bbrc.1996.1816.
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.
一氧化氮可导致RAW 264.7巨噬细胞发生凋亡性细胞死亡。细胞对一氧化氮供体S-亚硝基谷胱甘肽（GSNO）的反应包括凋亡形态和DNA片段化，这在很大程度上取决于肿瘤抑制基因产物p53的积累。在NG-单甲基-L-精氨酸（NMMA）存在的情况下，用脂多糖（LPS）、γ干扰素对巨噬细胞进行预处理可赋予其对通常由外源性供应的GSNO引发的凋亡性细胞死亡的抗性。同样，用低剂量GSNO（25 - 200微摩尔）预处理可使细胞对第二次更高剂量GSNO（1毫摩尔）的暴露产生抗性。这种保护作用在p53积累受阻的层面上得以体现。对非致死性一氧化氮浓度或通过脂多糖、细胞因子预刺激而产生的保护机制上调，可能会改变一氧化氮上调p53以及引发巨噬细胞凋亡的能力，从而调节细胞对一氧化氮中毒的易感性。
