Protein Thiol Redox Signaling in Monocytes and Macrophages.
Protein Thiol Redox Signaling in Monocytes and Macrophages.
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DOI：
10.1089/ars.2016.6697
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发表时间：
2016-11
影响因子：
6.6
通讯作者：
John D. Short;K. Downs;S. Tavakoli;R. Asmis
中科院分区：
文献类型：
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作者：
John D. Short;K. Downs;S. Tavakoli;R. Asmis
单核细胞和巨噬细胞功能障碍在广泛的炎症性疾病过程中起关键作用，包括肥胖、伤口愈合受损、糖尿病并发症和动脉粥样硬化。新出现的证据表明，单核细胞或巨噬细胞失调的最早期事件包括活性氧产生升高、巯基修饰和氧化还原敏感性信号通路的破坏。本文综述了单核细胞和巨噬细胞中巯基氧化还原信号的研究现状，包括（i）可逆的蛋白质-S-谷胱甘肽化发生的分子机制，（ii）在生理条件下发生的真正的S-谷胱甘肽化蛋白质的鉴定，以及（iii）巯基氧化还原信号的破坏如何影响单核细胞和巨噬细胞的功能，并有助于动脉粥样硬化。最新进展：氧化还原生物化学和生物学以及氧化还原蛋白质组学技术的最新进展导致许多新的巯基氧化还原调节蛋白和途径的鉴定。此外，在扩大S-谷胱甘肽化蛋白的列表和评估蛋白-S-谷胱甘肽化和S-谷胱甘肽化调节酶在单核细胞和巨噬细胞功能中发挥的作用方面取得了重大进展，包括单核细胞迁移、巨噬细胞极化、泡沫细胞形成和巨噬细胞死亡。关键问题单核细胞和巨噬细胞中的蛋白-S-谷胱甘肽化/去谷胱甘肽化已成为一种新的重要信号传导模式，为代谢紊乱、氧化应激和心血管疾病之间的关系提供了分子基础。未来的发展方向特异性S-谷胱甘肽化蛋白的鉴定以及单核细胞和巨噬细胞中控制这种翻译后蛋白修饰的机制将促进新的预防和治疗策略的发展，以对抗动脉粥样硬化和其他代谢性疾病。抗氧化剂。氧化还原信号。25，816-835。
SIGNIFICANCE Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death. CRITICAL ISSUES Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases. FUTURE DIRECTIONS The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal. 25, 816-835.