摘要
氧化性损伤与老化及人类一系列疾病有关。线粒体主要负责了产生自由基,它们也是这些有毒分子的主要攻击目标。抗氧化剂可以防止线粒体损伤带来的不良后果。褪黑激素是一种内源型的吲哚胺,它可以调节包括线粒体相关功能在内的各种功能;这是它的由其两亲性质的渗透所有形态生理学障碍并进入亚细胞区室的能力决定的。此外,该吲哚胺及其代谢产物是强力的抗氧化剂和自由基清除剂,能保护细胞膜、电子传递链和线粒体的DNA免受氧化性损伤。这些特性使得褪黑激素成为对抗与自由基相关的疾病的强力保护者。通过比较,其它传统抗氧化剂因难以到达线粒体而疗效较差。近年来,研究主要集中于线粒体靶向抗氧化剂的改进,如MitoQ(由亲脂性三苯基磷阳离子与内源抗氧化剂辅酶Q10通过共价结合组成)和MitoE(把三苯基磷阳离子与抗氧化剂α-生育酚连接组成)。以线粒体靶向抗氧化剂在线粒体内积累了几百倍浓度,并保护这些细胞器免受氧化性损伤。褪黑激素也是线粒体靶向抗氧化剂,具有与合成抗氧化剂相似的保护作用。仍需进一步研究来确定这些抗氧化剂在改善线粒体功能障碍相关疾病的治疗效能。
关键词: 线粒体,氧化应激,褪黑激素,以线粒体靶向的抗氧化剂,mitoQ,mitoE。
Current Medicinal Chemistry
Title:Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review
Volume: 22 Issue: 22
Author(s): M. R. Ramis, S. Esteban, A. Miralles, Dun-Xian Tan and R. J. Reiter
Affiliation:
关键词: 线粒体,氧化应激,褪黑激素,以线粒体靶向的抗氧化剂,mitoQ,mitoE。
摘要: Oxidative damage is related to aging and a wide range of human disorders. Mitochondria are in large part responsible for free radical production and they are also main targets of the attack of these toxic molecules. The resulting deleterious effects of the damage to mitochondria can be prevented by antioxidants. Melatonin is an endogenouslyproduced indoleamine that modulates numerous functions, including mitochondria-related functions; this result from its capacity to penetrate all morphophysiological barriers and to enter all subcellular compartments due to its amphiphilic nature. Furthermore, this indoleamine and its metabolites are powerful antioxidants and scavengers of free radicals, protecting cellular membranes, the electron transport chain and mitochondrial DNA from oxidative damage. These properties may make melatonin a potent protector against a variety of free radical-related diseases. By comparison, other conventional antioxidants have less efficacy due to their limited access to the mitochondria. In recent years, research has focused on the advancement of mitochondria-targeted antioxidants, such as MitoQ (composed by the lipophilic triphenylphosphonium cation conjugated to the endogenous antioxidant coenzyme Q10) and MitoE (composed by the triphenylphosphonium cation attached to the antioxidant α-tocopherol). Mitochondria-targeted antioxidants accumulate in several hundred-fold greater concentrations within mitochondria and protect these critical organelles from oxidative damage. Melatonin also seems to be a mitochondria-targeted antioxidant and has similar protective actions as the synthetic antioxidants. Further work is required to determine the therapeutic properties of these antioxidants in ameliorating diseases related to mitochondrial dysfunction.
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Cite this article as:
M. R. Ramis, S. Esteban, A. Miralles, Dun-Xian Tan and R. J. Reiter , Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review, Current Medicinal Chemistry 2015; 22 (22) . https://dx.doi.org/10.2174/0929867322666150619104143
DOI https://dx.doi.org/10.2174/0929867322666150619104143 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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