MnSOD, ROS, mitochondria, oxidative stress diseases and aging, superoxide theory
J Clin Biochem Nutr. 2015 Jan;56(1):1-7.
A mitochondrial superoxide theory for oxidative stress diseases and aging.
Indo HP1, Yen HC2, Nakanishi I3, Matsumoto K3, Tamura M4, Nagano Y4, Matsui H4, Gusev O5, Cornette R6, Okuda T6, Minamiyama Y7, Ichikawa H8, Suenaga S9, Oki M10, Sato T9, Ozawa T11, Clair DK12, Majima HJ13.
1Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40506, USA.
2Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan.
3Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
4Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
5Department of Invertebrates Zoology and Functional Morphology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremevskaya str., 17 Kazan 420-008, Russia ; Japan Aerospace Exploration Agency, Institute of Space and Astronautical Science, ISS Science Project Office, Ibaraki 305-8505, Japan ; Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
6Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
7Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan.
8Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshishia University, Kyoto 610-0394, Japan.
9Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
10Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
11Division of Oxidative Stress Research, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
12Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40506, USA.
13Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
Abstract
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.
