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理解细胞氧化还原稳态:精准医学的挑战。

Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine.

机构信息

Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, 1090 Vienna, Austria.

出版信息

Int J Mol Sci. 2021 Dec 22;23(1):106. doi: 10.3390/ijms23010106.

Abstract

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term "oxidative stress" is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.

摘要

生物体利用大量的合成代谢和分解代谢反应来维持其生理功能,其中许多反应包括底物的氧化和还原。氧化还原生物学领域试图了解氧化还原平衡是如何调节和维持的,以及在疾病的各种病理发展中哪些机制发生了偏离,其中氧化或还原应激是一个问题。“氧化应激”一词的定义是氧化剂的产生与局部抗氧化防御之间的不平衡。氧化应激的关键介质是来自氧、氮和硫的活性物质,它们在生理浓度下是信号因子,但当它们积累时会损伤细胞大分子。然而,在疾病中针对氧化应激的治疗比预期的要困难得多。造成这种情况的主要原因是细胞内氧化还原系统非常精细,它们在亚细胞区室中的浓度不同,并且取决于细胞和细胞器的生理或病理状态(即昼夜节律、细胞周期、代谢需求、疾病阶段)。由于活性物质被用作信号分子,在许多情况下,非靶向的广谱抗氧化剂将无法达到其治疗目的。精准医学被呼吁来改善这种情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69cc/8745322/8a1d4dee9ca2/ijms-23-00106-g001.jpg

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