Redox signaling regulated by electrophiles and reactive sulfur species.
Redox signaling regulated by electrophiles and reactive sulfur species.
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DOI：
10.3164/jcbn.15-111
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发表时间：
2016-03
影响因子：
2.4
通讯作者：
Akaike T
中科院分区：
文献类型：
--
作者：
Nishida M;Kumagai Y;Ihara H;Fujii S;Motohashi H;Akaike T
氧化还原信号是活性氧产生的生物分子非特异性损伤诱导的氧化应激的关键调节剂。当前的氧化还原生物学正在重新审视氧化应激的传统概念，即活性氧的毒性作用受到多种抗氧化系统的保护，这些抗氧化系统通过氧化应激反应上调，而氧化应激反应是由氧化还原依赖性细胞信号传导途径生理介导的。因此，氧化还原信号传导受到应激反应过程中活性氧和一氧化氮及其衍生活性物质产生的内源性亲电子物质的精确调节。在内源形成的亲电子试剂中，8-硝基鸟苷3',5'-环单磷酸（8-硝基-cGMP）具有独特的细胞信号传导功能，其生物合成、信号传导机制和细胞内代谢途径已被阐明。细胞中丰富的活性硫物质，例如半胱氨酸氢过硫化物，可能参与 8-硝基-cGMP 代谢。氧化还原生物学的这些新方面可能会刺激细胞和干细胞生物学的创新和多学科研究；传染病、癌症、代谢综合征、衰老和神经退行性疾病；和其他氧化应激相关疾病。本综述重点关注 8-硝基-cGMP 生物合成、细胞信号传导和代谢方面的最新进展，8-硝基-cGMP 可能是药物开发的目标，并导致许多疾病的新疗法的发现。
Redox signaling is a key modulator of oxidative stress induced by nonspecific insults of biological molecules generated by reactive oxygen species. Current redox biology is revisiting the traditional concept of oxidative stress, such that toxic effects of reactive oxygen species are protected by diverse antioxidant systems upregulated by oxidative stress responses that are physiologically mediated by redox-dependent cell signaling pathways. Redox signaling is thus precisely regulated by endogenous electrophilic substances that are generated from reactive oxygen species and nitric oxide and its derivative reactive species during stress responses. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive sulfur species such as cysteine hydropersulfides that are abundant in cells are likely involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cell and stem cell biology; infectious diseases, cancer, metabolic syndrome, ageing, and neurodegenerative diseases; and other oxidative stress-related disorders. This review focuses on the most recent progress in the biosynthesis, cell signaling, and metabolism of 8-nitro-cGMP, which is a likely target for drug development and lead to discovery of novel therapeutics for many diseases.