A mitochondrial superoxide theory for oxidative stress diseases and aging.

A mitochondrial superoxide theory for oxidative stress diseases and aging.
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DOI:
10.3164/jcbn.14-42
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发表时间:
2015-01
影响因子:
2.4
通讯作者:
Majima HJ
Majima HJ
中科院分区:
医学4区
文献类型:
--
作者:
Indo HP;Yen HC;Nakanishi I;Matsumoto K;Tamura M;Nagano Y;Matsui H;Gusev O;Cornette R;Okuda T;Minamiyama Y;Ichikawa H;Suenaga S;Oki M;Sato T;Ozawa T;Clair DK;Majima HJ

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Fridovich于1969年发现了CuZnSOD,并于1973年发现了锰超氧化物歧化酶(MnSOD),并提出了“超氧化物理论”,该理论假设超氧化物(O2•−)是大多数活性氧(ROS)的起源,并且它在细胞中发生链式反应,在ROS产生系统中发挥核心作用。生物体氧化应激的增加会对细胞(生物体的最小组成单位)造成损害,从而导致多种慢性疾病的发生,例如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症以及其他由生物防御异常或细胞内活性氧水平升高引起的神经系统疾病。氧化应激也在衰老中发挥作用。抗氧化系统,包括非酶低分子量抗氧化剂(例如维生素 A、C 和 E、多酚、谷胱甘肽和辅酶 Q10)和抗氧化酶,可对抗细胞中的氧化剂。超氧化物被认为是氧化剂毒性的主要因素,而线粒体 MnSOD 酶构成了针对超氧化物的重要防御。线粒体是超氧化物的主要来源。线粒体产生的超氧化物与一氧化氮的反应比SOD催化的反应更快,并产生过氧亚硝酸盐。因此,基于弗里多维奇开创性研究之后进行的研究,我们现在提出了一种改进的超氧化物理论;也就是说,超氧化物是活性氧和活性氮(RONS)的来源,因此会导致各种氧化还原相关疾病和衰老。
Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
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DOI: 10.1002/j.1460-2075.1986.tb04256.x
发表时间: 1986-03-01
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影响因子: 11.4
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