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Role of 8-nitro-cGMP and its redox regulation in cardiovascular electrophilic signaling

机译:8-硝基-cGMP及其氧化还原调节在心血管亲电信号中的作用

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摘要

Structural and morphological changes of the cardiovascular systems (cardiovascular remodeling) are a major clinical outcome of cardiovascular diseases. Many lines of evidences have implied that transfiguration of reduction/oxidation (redox) homeostasis due to excess production of reactive oxygen species (ROS) and/or ROS-derived electrophilic metabolites (electrophiles) is the main cause of cardiovascular remodeling. Gasotransmitters, such as nitric oxide (NO) and endogenous electrophiles, are considered major bioactive species and have been extensively studied in the context of physiological and pathological cardiovascular events. We have recently found that hydrogen sulfide-related reactive species function as potent nucleophiles to eliminate electrophilic modification of signaling proteins induced by NO-derived electrophilic byproducts (e.g., 8-nitroguanosine 3',5'-cyclic monophosphate and nitro-oleic acid). In this review, we discuss the current understanding of redox control of cardiovascular pathophysiology by electrophiles and nucleophiles. We propose that modulation of electrophile-mediated post-translational modification of protein cysteine thiols may be a new therapeutic strategy of cardiovascular diseases. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".
机译:心血管系统的结构和形态变化(心血管重塑)是心血管疾病的主要临床结果。许多证据表明,由于过量生产活性氧(ROS)和/或ROS衍生的亲电子代谢产物(electrophiles)而引起的还原/氧化(redox)稳态的变形是心血管重塑的主要原因。一氧化氮(NO)和内源性亲电子试剂等气体递质被认为是主要的生物活性物种,并已在生理和病理性心血管事件中进行了广泛研究。我们最近发现,与硫化氢有关的反应性物质起有效的亲核试剂的作用,以消除由NO衍生的亲电副产物(例如8-硝基鸟苷3',5'-环一磷酸和硝基​​油酸)诱导的信号蛋白的亲电修饰。在这篇综述中,我们讨论了目前由亲电试剂和亲核试剂对氧化还原控制心血管病理生理的认识。我们建议调节亲电体介导的蛋白质半胱氨酸硫醇翻译后修饰的修饰可能是心血管疾病的一种新的治疗策略。本文是名为“心血管系统中的氧化还原信号传递”的特刊的一部分。

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