Vascular Antioxidant Defense Systems

Living organisms have evolved a number of antioxidant defense mechanisms, both enzymatic and nonenzymatic, to maintain their survival against oxidative stress.24,32,80 Major antioxidant enzymes in the vessel wall include SOD, cata-lase, and glutathione peroxidase, whereas nonenzymatic sources include small molecules and vitamins.24,80 Three mammalian SODs have been identified: copper/zinc SOD (SOD1), mitochondrial MnSOD (SOD2), and extracellular SOD (SOD3).24 The concentration of SOD in the extracellular fluid is lower than in the intracellular fluid. Therefore *O2- can survive longer and travel further once it gains access to the extracellular space. Arteries contain large amounts of extracellular SOD in the interstitium, suggesting a special role for this SOD isoform within the vessel wall.81,82 SOD converts *O2- to H2O2, which is hydrolyzed by catalase and glutathione peroxidase to H2O and O2. Glutathione peroxidase is the major enzyme protecting the cell membrane against lipid peroxidation, since reduced glutathione (GSH) donates protons to membrane lipids maintaining them in a reduced state. In addition to endogenous enzyme antioxi-dants, numerous nonenzymatic antioxidants are found in biological systems. Scavenging antioxidants include ascorbic acid (vitamin C), a-tocopherol (vitamin E), flavonoids, carotenoids, bilirubin, and thiols.83 Ascorbic acid is water-soluble, whereas a-tocopherol and P-carotene are lipid-soluble. Metal-binding proteins, such as hemoglobin, myoglobin, transferrin, ferritin, and ceruloplasmin are involved in reducing OH- formation. Decreased bioavailability of antioxi-dants results in accumulation of oxygen intermediates and consequent increased oxidative stress. Based on this paradigm it has been suggested that antioxidant supplementation may have beneficial therapeutic effects in reducing oxidative stress in disease process.

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