GSH peroxidase

A variety of other metals and their complexes have been studied for radioprotective activity. Among these are copper glycinate, strontium chloride, ZnNa -diethylenetriaminepentaacetate (ZnDTPA), and selenium, which has been studied because of its relationship to endogenous antioxidant mechanisms, especiaHy GSH peroxidase and vitamin E. 

GSH peroxidase Liver Surf scoter, ruddy duck No Decreased Hoffman et al. (1998)... 

The enzymes GSH peroxidase, GSH reductase and SOD collaborate to ensure that the red cell is protected from the effects of methaemoglobin and superoxide. Disposal of hydrogen peroxide may occur by catalase, in a reaction which is also dependent on NADPH. This vital coenzyme is provided via the PPP. Although the PPP operates in all cell types for the provision of pentose sugars and nucleotides, its role in the RBC is more directed to cell survival than cell division. 

The BEAS-2B cell line has been described previously as retaining the expression of most of the phase II enzymes (i.e., epoxide hydrolase, GST pi, GSH peroxidase and catalase) [121], However, when Kuzuya and co-workers quantitatively compared UGT levels amongst NHBE, Calu-3 and BEAS-2B cells, the Calu-3 cell line showed expression levels most comparable to NHBE, while results from BEAS-2B cells were significantly different from others (Table 10.2) [116],... 

The hepatocytes, or parenchymal cells, represent about 80% of the liver by volume and are the major source of metabolic activity. However, this metabolic activity varies depending on the location of the hepatocyte. Thus, zone 1 hepatocytes are more aerobic and therefore are particularly equipped for pathways such as the p-oxidation of fats, and they also have more GSH and GSH peroxidase. These hepatocytes also contain alcohol dehydrogenase and are able to metabolize allyl alcohol to the toxic metabolite acrolein, which causes necrosis in zone 1. Conversely, zone 3 hepatocytes have a higher level of cytochromes P-450 and NADPH cytochrome P-450 reductase, and lipid synthesis is higher in this area. This may explain why zone 3 is most often damaged, and lipid accumulation is a common response (see "Carbon Tetrachloride," for instance, chap. 7). 

The hydrogen peroxide produced by SOD is then removed by either catalase action or GSH peroxidase. The products are water and oxygen or water and GSSG (Figs. 6.10 and 6.18). 

Lipid hydroperoxides can be removed by reaction with GSH catalyzed by GSH peroxidase. The enzyme phospholipase A2 has been proposed to have a role in the detoxication of phospholipid hydroperoxides by releasing fatty acids from peroxidized membranes. 

However, the reactive metabolite will cause other changes as well as binding to protein. Thus, NAPQI will react both chemically and enzymatically with GSH to form a conjugate and will also oxidize it to GSSG and in turn be reduced back to paracetamol. This cyclical process may explain the occurrence of extensive depletion of GSH. NADPH will also reduce NAPQI and in turn be oxidized to NADP, although reduction via GSH is probably preferential. NADPH oxidation may also result from GSSG reduction via GSH peroxidase (Fig. 7.18). 

The heart has reduced levels of antioxidants such as GSH, GSH peroxidase, superoxide dismutase, and catalase and is therefore vulnerable to attack by ROS. 

GSH, a tripeptide of glutamic acid, cysteine, and glycine (GluCysGly), is the major water-soluble antioxidant in the cytoplasm, nuclei, and mitochondria of cells. Many of the critical antioxidant functions of GSH require GSH peroxidase, which exists in several forms. Reduction of oxidized GSH (GSH disulfide), which is produced by reactions involving GSH peroxidase, requires GSH reductase. 

Although inorganic selenium does not have antioxidant properties, selenium has an important role in cellular antioxidant defenses as a necessary component of selenoproteins. Selenium is incorporated into selenoproteins as selenocysteine. The glutathione (GSH) peroxidases are the best-characterized selenoproteins, although other circulating selenoproteins also have antioxidant functions. 

Parenteral administration of 27 to 60 jLig/kg of selenium to laboratory animals has been shown to inhibit doxorubicin-induced decreases in myocardial vitamin E and GSH peroxidase levels and to reduce changes in myocardial function that are consistent with acute doxorubicin-induced cardiotoxicity. Oral supplementation of sodium selenite also protects against acute doxorubicin-induced cardiotoxicity in rabbits. 

Several studies have explored SOD activity in peripheral tissues of patients with Parkinson s disease as potential markers of oxidative stress, and have yielded inconsistent results. Elevations of total (combined Cu,Zn-SOD and Mn-SOD) SOD activity and GSH peroxidase activity in serum of patients with Parkinson s disease have been reported. Furthermore, elevations of immunoreactive Mn-SOD in cerebrospinal fluid of patients with Parkinson s disease but normal levels of Cu,Zn-SOD have been detected. Erythrocyte SOD activity, which is exclusively due to Cu,Zn-SOD, is unaltered in Parkinson s disease. Moreover, no differences in mean activities of total SOD, GSH peroxidase, GSH reductase, or catalase have been detected in either the lymphocytes, granulocytes, or cerebrospinal fluid of patients with Parkinson s disease. 

Table IV. Dietary Vitamin E and GSH Peroxidase System in the Lungs of Cigarette-Smoked Rats ...

Popovid et al. (2007) studied the in vitro and in vivo antioxidant activity of the different extracts of the leaves and root of parsley. All extracts were good scavengers of DPPH and OH radicals and reduced the intensity of lipid peroxidation in vitro. The in vivo effects were evaluated on some antioxidant systems (activities of lipid peroxidase, GSH-peroxidase, peroxidase, catalase and xanthine oxidase and GSH content) in mice liver and blood after treatment with the examined parsley extracts, or in combination with carbon tetrachloride (CC14). On the basis of the results obtained, it can be concluded that the examined extracts exhibited a certain protective effect. However, combined treatments with CC14 and the examined extracts showed both positive... 

S. Braddon-Galloway, J. E. Balthrop, Se-dependent GSH-peroxidase isolated from Black Sea Bass (Centropristis striata), Comp. Biochem. Physiol., 82C (1985), 297-300. 

Fig. 1. Enzyme activities in homogenates of control and UVA-treated skin. Catalase, mmol oxygen/ mgprotein/min GSH reductase, nmol GSH/mgprotein/min GSH peroxidase, nmolNADPH/ mg protein/min SOD, U/mg protein. Mean values SEM are shown. Statistically lower than unirradiated controls double asterisks, p < 0.01 single asterisk, p < 0.05.

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