Nishida Motohiro, Nishimura Akiyuki, Matsunaga Tetsuro, Motohashi Hozumi, Kasamatsu Shingo, Akaike Takaaki
Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan; Department of Translational Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; PRESTO, Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan.
Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan.
Free Radic Biol Med. 2017 Aug;109:132-140. doi: 10.1016/j.freeradbiomed.2017.01.024. Epub 2017 Jan 18.
Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. 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 persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease.
通过精确控制系统维持氧化还原平衡，该系统调节亲电物质（亲电试剂）的产生、消除和代谢，这对正常心血管功能至关重要。亲电信号主要受内源性亲电试剂调节，这些亲电试剂在应激反应期间由活性氧、一氧化氮以及一氧化氮的衍生活性物质产生，同时也受外源性亲电试剂调节，包括食物中的化合物和环境污染物。在细胞内源性形成的亲电试剂中，8-硝基鸟苷3',5'-环一磷酸（8-硝基-cGMP）具有独特的细胞信号功能，其生物合成途径、信号机制以及在细胞内的代谢过程已得到阐明。细胞内源性产生的反应性过硫化物，如半胱氨酸过硫化物和多硫化物，可能参与8-硝基-cGMP的代谢。氧化还原生物学的这些新方面可能会激发心血管生理学和病理生理学领域的创新性多学科研究。在我们的综述中，我们重点关注心肌细胞中反应性过硫化物通过亲电试剂的还原和代谢对亲电信号进行的氧化还原依赖性调节，并提出心血管疾病新治疗策略的建议。
