Peroxynitrite modulates MnSOD gene expression in lung epithelial cells.
Peroxynitrite modulates MnSOD gene expression in lung epithelial cells.
复制标题
过氧亚硝酸盐调节肺上皮细胞中的 MnSOD 基因表达。
DOI：
10.1016/s0891-5849(98)00101-4
复制
发表时间：
1998
影响因子：
7.4
通讯作者：
Helton,ES
中科院分区：
文献类型：
--
作者：
Jackson,RM;Parish,G;Helton,ES
过氧亚硝酸盐（ONOO −）是一种强氧化剂，来源于炎症组织中存在的一氧化氮（NO）和超氧化物（O2·−），活性氮（RNS）和氧物种（ROS）。其他氧化应激，例如，TNF-α和高氧诱导线粒体含锰超氧化物歧化酶（MnSOD）基因表达。这些实验测试了ONOO −是否调节人肺上皮细胞（A549）中MnSOD基因的表达。3-SIN-1（10或1000 μ M）可增加MnSOD mRNA的表达，但对次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）mRNA的表达无影响。真正的过氧亚硝酸盐（ONOO −）（100 - 500 μ M）也增加了MnSOD mRNA，但没有改变组成型HPRT mRNA的表达。ONOO −刺激荧光素酶基因表达，由大鼠MnSOD基因5 ′启动子区的2.5 kb片段驱动。MnSOD基因诱导由于ONOO −有效地抑制L-半胱氨酸（10 mM）和部分抑制N-乙酰半胱氨酸（50 mM）或吡咯二硫代氨基甲酸酯（10 mM）。1-丙胺、3-（2-羟基-2-亚硝基-1-丙基肼）（PAPA NONOate）（100或1000 μ M）中的NO未改变MnSOD或HPRT mRNA。SIN-1和ONOO-的分解产物H2O2和NO2-对MnSOD mRNA表达没有任何影响;然而，ONOO-和SIN-1没有增加MnSOD蛋白质含量，也没有增加MnSOD酶活性。在NO存在下，稳态[O2·−]增加产生ONOO −，ONOO −对MnSOD转录本表达具有直接的刺激作用。
Peroxynitrite (ONOO−) is a strong oxidant derived from nitric oxide (NO) and superoxide (O2•−), reactive nitrogen (RNS) and oxygen species (ROS) present in inflamed tissue. Other oxidant stresses, e.g., TNF-α and hyperoxia, induce mitochondrial, manganese-containing superoxide dismutase (MnSOD) gene expression. These experiments tested whether ONOO−regulated MnSOD gene expression in human lung epithelial (A549) cells. 3-morpholinosydnonimine HCl (SIN-1) (10 or 1000 μM) increased MnSOD mRNA, but did not change hypoxanthine guanine phosphoribosyl transferase (HPRT) mRNA. Authentic peroxynitrite (ONOO−) (100–500 μM) also increased MnSOD mRNA but did not change constitutive HPRT mRNA expression. ONOO−stimulated luciferase gene expression driven by a 2.5 kb fragment of the rat MnSOD gene 5′ promoter region. MnSOD gene induction due to ONOO−was inhibited effectively by L-cysteine (10 mM) and partially inhibited by N-acetyl cysteine (50 mM) or pyrrole dithiocarbamate (10 mM). NO from 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazine) (PAPA NONOate) (100 or 1000 μM) did not change MnSOD or HPRT mRNA. Neither H2O2nor NO2−, breakdown products of SIN-1 and ONOO−, had any effect on MnSOD mRNA expression; however, ONOO−and SIN-1 did not increase MnSOD protein content detectable by western blots, nor did they increase MnSOD enzymatic activity. Increased steady state [O2•−] in the presence of NO yields ONOO−, and ONOO−has direct, stimulatory effects on MnSOD transcript expression.