Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation
Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation
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DOI：
10.1006/bbrc.1997.7672
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发表时间：
1997-11-17
影响因子：
3.1
通讯作者：
Kim, YM
中科院分区：
文献类型：
--
作者：
Li, JR;Billiar, TR;Kim, YM
半胱天冬酶是一个由至少 10 种人类半胱氨酸蛋白酶组成的家族，参与细胞因子成熟以及细胞凋亡信号转导和执行机制。这些酶的肽抑制剂能够阻断细胞因子成熟和细胞凋亡，证明它们在这些过程中的关键作用。我们最近发现，一氧化氮（NO）无论是由NO供体在细胞外产生还是由诱导型一氧化氮合酶在细胞内产生，都可以防止肝细胞凋亡。发现在这些条件下，Caspase-3 样活性受到抑制。为了进一步研究 NO 和 caspase 之间的相互作用，我们利用纯化的人重组 caspase 并检查 NO 对不同 caspase 酶活性的影响。我们在此报告，在所研究的七种半胱天冬酶中，全部都被 NO 可逆地抑制。二硫苏糖醇能够逆转 NO 抑制，表明 NO 对 caspase 催化半胱氨酸残基进行直接 S-亚硝基化。我们的结果支持这样的概念：NO 是 caspase 活性的内源性调节剂。 (C) 1997 年学术出版社。
The caspases are a family of at least 10 human cysteine proteases that participate in cytokine maturation and in apoptotic signal transduction and execution mechanisms. Peptidic inhibitors of these enzymes are capable of blocking cytokine maturation and apoptosis, demonstrating their crucial roles in these processes. We have recently discovered that nitric oxide (NO), produced either extracellularly by NO donors or intracellularly by the inducible nitric oxide synthase, prevented apoptosis in hepatocytes. Caspase-3-like activity was found to be inhibited under these conditions. To investigate further the interaction between NO and caspases, we utilized purified human recombinant caspases and examined the effect of NO on enzymatic activities of different caspases. We report here that of the seven caspases studied, all were reversibly inhibited by NO. Dithiothreitol was able to reverse the NO inhibition, indicating direct S-nitrosylation of caspase catalytic cysteine residue by NO. Our results support the concept that NO is an endogenous regulator of caspase activity. (C) 1997 Academic Press.