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细胞生物学中的S-亚硝基化信号传导

S-nitrosylation signaling in cell biology.

作者信息

Gaston Benjamin M, Carver Jeannean, Doctor Allan, Palmer Lisa A

机构信息

Department of Pediatrics, Division of Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908 USA.

出版信息

Mol Interv. 2003 Aug;3(5):253-63. doi: 10.1124/mi.3.5.253.

DOI:10.1124/mi.3.5.253
PMID:14993439
Abstract

S-Nitrosylated proteins form when a cysteine thiol reacts with nitric oxide (NO) in the presence of an electron acceptor to form an S-NO bond. Under physiological conditions, this posttranslational modification affects the function a wide array of cell proteins, ranging from ion channels to nuclear regulatory proteins. Recent evidence suggests that 1) S-nitrosylated proteins can be synthesized by exposure of specific redox-active motifs to NO, through transnitrosation/transfer reactions, or through metalloprotein-catalyzed reactions; 2) S-nitrosothiols can be sequestered in membranes, lipophilic protein folds, or in vesicles to preserve their activity; and 3) S-nitrosothiols can be degraded by a number of enzymes systems. These recent insights regarding the bioactivities, molecular signaling pathways, and metabolism of endogenous S-nitrosothiols have suggested several new therapies for disease ranging from cystic fibrosis to pulmonary hypertension.

摘要

当半胱氨酸硫醇在电子受体存在的情况下与一氧化氮(NO)反应形成S-NO键时,就会形成S-亚硝基化蛋白。在生理条件下,这种翻译后修饰会影响多种细胞蛋白的功能,从离子通道到核调节蛋白。最近的证据表明:1)S-亚硝基化蛋白可以通过特定的氧化还原活性基序暴露于NO、通过转亚硝基化/转移反应或通过金属蛋白催化反应来合成;2)S-亚硝基硫醇可以被隔离在膜、亲脂性蛋白折叠结构或囊泡中以保持其活性;3)S-亚硝基硫醇可以被多种酶系统降解。这些关于内源性S-亚硝基硫醇的生物活性、分子信号通路和代谢的最新见解为从囊性纤维化到肺动脉高压等疾病提出了几种新的治疗方法。

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