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A mitochondrial superoxide theory for oxidative stress diseases and aging.

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 - J Clin Biochem Nutr (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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.

No MeSH data available.


Related in: MedlinePlus

Ultrastructural analysis of cells cultured at pH 8.3 for 6 h. Electron microscopy of (a) SOD transfected cells that appear normal with normal mitochondria (arrow) and (b) NEO cells show accumulation of lysosomes with membrane debris observed internally (arrow). The cell surface demonstrates prominent membrane blebs (arrowhead). Mitochondria show focal swelling and loss of cristae. Focal condensation of chromosomal material is present. This research was originally published in J Biol Chem., Majima HJ, Oberley TD, Furukawa K, Mattson MP, Yen H-C, Szweda LI, St Clair DK: Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. J Biol Chem 1998; 273: 8217–8224. Reprint from ref. 9 with permission.
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Figure 5: Ultrastructural analysis of cells cultured at pH 8.3 for 6 h. Electron microscopy of (a) SOD transfected cells that appear normal with normal mitochondria (arrow) and (b) NEO cells show accumulation of lysosomes with membrane debris observed internally (arrow). The cell surface demonstrates prominent membrane blebs (arrowhead). Mitochondria show focal swelling and loss of cristae. Focal condensation of chromosomal material is present. This research was originally published in J Biol Chem., Majima HJ, Oberley TD, Furukawa K, Mattson MP, Yen H-C, Szweda LI, St Clair DK: Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. J Biol Chem 1998; 273: 8217–8224. Reprint from ref. 9 with permission.

Mentions: Free radicals generated from mitochondria could play a role in many kinds of cell death; i.e., apoptosis, necrosis, autophagy.(83,84) In our published paper that reported the relationship between ROS generated from mitochondria and apoptosis,(9) we showed an electron microscopic picture of mitophagy impacted by an alkaline condition, whereas MnSOD transfected cells seemed normal, as shown in Fig. 5. These findings indicate that MnSOD is essential for maintenance of life and cellular resistance to oxidative stress in the presence of oxygen, and suggest that superoxide generated from mitochondria plays an important role in oxidative stress and its related diseases, including aging.


A mitochondrial superoxide theory for oxidative stress diseases and aging.

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 - J Clin Biochem Nutr (2014)

Ultrastructural analysis of cells cultured at pH 8.3 for 6 h. Electron microscopy of (a) SOD transfected cells that appear normal with normal mitochondria (arrow) and (b) NEO cells show accumulation of lysosomes with membrane debris observed internally (arrow). The cell surface demonstrates prominent membrane blebs (arrowhead). Mitochondria show focal swelling and loss of cristae. Focal condensation of chromosomal material is present. This research was originally published in J Biol Chem., Majima HJ, Oberley TD, Furukawa K, Mattson MP, Yen H-C, Szweda LI, St Clair DK: Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. J Biol Chem 1998; 273: 8217–8224. Reprint from ref. 9 with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4306659&req=5

Figure 5: Ultrastructural analysis of cells cultured at pH 8.3 for 6 h. Electron microscopy of (a) SOD transfected cells that appear normal with normal mitochondria (arrow) and (b) NEO cells show accumulation of lysosomes with membrane debris observed internally (arrow). The cell surface demonstrates prominent membrane blebs (arrowhead). Mitochondria show focal swelling and loss of cristae. Focal condensation of chromosomal material is present. This research was originally published in J Biol Chem., Majima HJ, Oberley TD, Furukawa K, Mattson MP, Yen H-C, Szweda LI, St Clair DK: Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. J Biol Chem 1998; 273: 8217–8224. Reprint from ref. 9 with permission.
Mentions: Free radicals generated from mitochondria could play a role in many kinds of cell death; i.e., apoptosis, necrosis, autophagy.(83,84) In our published paper that reported the relationship between ROS generated from mitochondria and apoptosis,(9) we showed an electron microscopic picture of mitophagy impacted by an alkaline condition, whereas MnSOD transfected cells seemed normal, as shown in Fig. 5. These findings indicate that MnSOD is essential for maintenance of life and cellular resistance to oxidative stress in the presence of oxygen, and suggest that superoxide generated from mitochondria plays an important role in oxidative stress and its related diseases, including aging.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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.

No MeSH data available.


Related in: MedlinePlus