Nitric oxide causes ADP-ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase.
Nitric oxide causes ADP-ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase.
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DOI：
10.1016/s0021-9258(18)41847-9
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发表时间：
1992-08
期刊：
影响因子：
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通讯作者：
Stefanie DimmelerS;Friedrich LottspeichQ;Bernhard BriineSV
中科院分区：
文献类型：
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作者：
Stefanie DimmelerS;Friedrich LottspeichQ;Bernhard BriineSV
一氧化氮和一氧化氮生成剂，如3-吗啉-西诺亚胺(SIN-1)，在不同组织中刺激胞浆中39-kDa蛋白质的单-ADP-核糖化。用常规和快速蛋白质液相色谱技术从人血小板胞浆液中提纯了该蛋白。N端序列分析表明，该分离蛋白为糖酵解酶甘油醛-3-磷酸脱氢酶(GAPDH)。一氧化氮以时间和浓度依赖的方式刺激GAPDH的自身ADP核糖化，约60min后作用最强。与ADP-核糖化相关的是酶活性的丧失。SIN-1不抑制NAD(+)自由酶，表明NAD+作为ADP-核糖化反应的底物是绝对需要的。对糖酵解酶GAPDH的抑制可能与NO对呼吸链上的铁硫酶(如乌头酸酶和电子传递蛋白)的抑制作用互补的细胞毒性作用有关。
Nitric oxide and nitric oxide-generating agents like 3-morpholinosydnonimine (SIN-1) stimulate the mono-ADP-ribosylation of a cytosolic, 39-kDa protein in various tissues. This protein was purified from human platelet cytosol by conventional and fast protein liquid chromatography techniques. N-terminal sequence analysis identified the isolated protein as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Nitric oxide stimulates the auto-ADP-ribosylation of GAPDH in a time and concentration-dependent manner with maximal effects after about 60 min. Associated with ADP-ribosylation is a loss of enzymatic activity. NAD(+)-free enzyme is not inhibited by SIN-1, indicating the absolute requirement of NAD+ as the substrate of the ADP-ribosylation reaction. Inhibition of the glycolytic enzyme GAPDH may be relevant as a cytotoxic effect of NO complementary to its inhibitory actions on iron-sulfur enzymes like aconitase and electron transport proteins of the respiratory chain.