Messmer U K, Ankarcrona M, Nicotera P, Brüne B
University of Konstanz, Faculty of Biology, Germany.
FEBS Lett. 1994 Nov 21;355(1):23-6. doi: 10.1016/0014-5793(94)01161-3.
Nitric oxide (NO) is a diffusible messenger involved in several patho-physiological processes including immune-mediated cytotoxicity and neural cell killing. NO or the products of its redox chemistry can cause DNA damage and activate subsequent lethal reactions including energy depletion and cell necrosis. However, regardless of whether it is endogenously produced in response to cytokines, or generated by chemical breakdown of donor molecules, NO can also induce apoptosis in different systems. Here, we report that NO generation in response to a cytokine induced NO-synthase or by NO donors stimulates the expression of the tumor suppressor gene, p53, in RAW 264.7 macrophages or pancreatic RINm5F cells prior to apoptosis. NO-synthase inhibitors such as NG-monomethyl-L-arginine prevent the inducible NO generation as well as p53 expression and apoptosis. Since p53 expression is linked to apoptosis in some cells exposed to DNA damaging agents, we suggest that NO-induced apoptosis in these cell systems is the consequence of DNA damage and subsequent expression of this tumor suppressor gene.
一氧化氮（NO）是一种可扩散的信使分子，参与多种病理生理过程，包括免疫介导的细胞毒性作用和神经细胞杀伤。NO或其氧化还原化学反应的产物可导致DNA损伤，并激活随后的致死反应，包括能量耗竭和细胞坏死。然而，无论NO是内源性地响应细胞因子产生，还是由供体分子的化学分解产生，它在不同系统中也能诱导细胞凋亡。在此，我们报告，在RAW 264.7巨噬细胞或胰腺RINm5F细胞凋亡之前，由细胞因子诱导的一氧化氮合酶产生的NO或由NO供体产生的NO会刺激肿瘤抑制基因p53的表达。一氧化氮合酶抑制剂，如NG-单甲基-L-精氨酸，可阻止诱导型NO的产生以及p53的表达和细胞凋亡。由于p53的表达与一些暴露于DNA损伤剂的细胞中的细胞凋亡有关，我们认为在这些细胞系统中，NO诱导的细胞凋亡是DNA损伤以及随后该肿瘤抑制基因表达的结果。
