UNIPROT:P30044 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P30044 (antioxidant enzyme)
8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methionine is converted by the transmethylation/transsulfuration pathway to homocysteine which may exert atherogenic effects by several mechanisms, including lipid peroxidation. Therefore, the excessive dietary methionine may induce the development of atherosclerosis. To test this hypothesis, plasma and aortic thiobarbituric acid reactive substances (TBARS), as well as activities of aortic and erythrocyte superoxide dismutase (SOD), catalase and selenium-dependent glutathione peroxidase (GPX) were measured in rabbits fed a diet enriched with 0.3% methionine for 6 or 9 months. Histological examinations of aortas also were performed. Feeding rabbits a methionine-enriched diet for 6 or 9 months resulted in significant increases in plasma and aortic TBARS levels and aortic antioxidant enzyme activities. However, a decrease in plasma antioxidant activity (AOA) was observed. In erythrocytes, SOD activity increased, catalase remained normal and GPX decreased in the treated animals. Histological examination of aortas showed typical atherosclerotic changes, such as intimal thickening, deposition of cholesterol, and calcification in methionine-fed rabbits. These results confirm that high-methionine diet may induce atherosclerosis in rabbits and indicate disturbances in lipid peroxidation and antioxidant processes as possible mechanisms of its atherogenic influence.
...
PMID:Increased lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits. 766 80

Homocyst(e)ine (Hcy) inhibits the expression of the antioxidant enzyme cellular glutathione peroxidase (GPx-1) in vitro and in vivo, which can lead to an increase in reactive oxygen species that inactivate NO and promote endothelial dysfunction. In this study, we tested the hypothesis that overexpression of GPx-1 can restore the normal endothelial phenotype in hyperhomocyst(e)inemic states. Heterozygous cystathionine beta-synthase-deficient (CBS((-/+))) mice and their wild-type littermates (CBS((+/+))) were crossbred with mice that overexpress GPx-1 [GPx-1((tg+)) mice]. GPx-1 activity was 28% lower in CBS((-/+))/GPx-1((tg-)) compared with CBS((+/+))/GPx-1((tg-)) mice (P < 0.05), and CBS((-/+)) and CBS((+/+)) mice overexpressing GPx-1 had 1.5-fold higher GPx-1 activity compared with GPx-1 nontransgenic mice (P < 0.05). Mesenteric arterioles of CBS((-/+))/GPx-1((tg-)) mice showed vasoconstriction to superfusion with beta-methacholine and bradykinin (P < 0.001 vs. all other groups), whereas nonhyperhomocyst(e)inemic mice [CBS((+/+))/GPx-1((tg-)) and CBS((+/+))/GPx-1((tg+)) mice] demonstrated dose-dependent vasodilation in response to both agonists. Overexpression of GPx-1 in hyperhomocyst(e)inemic mice restored the normal endothelium-dependent vasodilator response. Bovine aortic endothelial cells (BAEC) were transiently transfected with GPx-1 and incubated with dl-homocysteine (HcyH) or l-cysteine. HcyH incubation decreased GPx-1 activity in sham-transfected BAEC (P < 0.005) but not in GPx-1-transfected cells. Nitric oxide release from BAEC was significantly decreased by HcyH but not cysteine, and GPx-1 overexpression attenuated this decrease. These findings demonstrate that overexpression of GPx-1 can compensate for the adverse effects of Hcy on endothelial function and suggest that the adverse vascular effects of Hcy are at least partly mediated by oxidative inactivation of NO.
...
PMID:Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. 1160 74

Homocystinuria is an inherited metabolic disease characterized biochemically by increased blood and brain levels of homocysteine caused by severe deficiency of cystathionine beta-synthase activity. Affected patients present mental retardation, seizures, and atherosclerosis. Oxidative stress plays an important role in the pathogenesis of many neurodegenerative and vascular diseases, such Alzheimer's disease, stroke, and atherosclerosis. However, the mechanisms underlying the neurological damage characteristic of homocystinuria are still poorly understood. To evaluate the involvement of oxidative stress on the neurological dysfunction present in homocystinuria, we measured thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and total radical-trapping antioxidant potential (TRAP) and antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) in rat hippocampus in the absence (controls) or in the presence of homocysteine (10-500 microM) in vitro. We demonstrated that homocysteine significantly increases TBARS and decreases TRAP, both in a dose-dependent manner, but did not change antioxidant enzymes. Our results suggest that oxidative stress is involved in the neurological dysfunction of homocystinuria. However, further studies are necessary to confirm and extend our findings to the human condition and also to determine whether antioxidant therapy may be of benefit to these patients.
...
PMID:In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. 1282 33

Hyperhomocysteinemia contributes to vascular dysfunction and an increase in the risk of cardiovascular disease. An elevated level of homocysteine in vivo and in cell culture systems results in a decrease in the activity of cellular glutathione peroxidase (GPx1), an intracellular antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides. In this study, we show that homocysteine interferes with GPx1 protein expression without affecting transcript levels. Expression of the selenocysteine (SEC)-containing GPx1 protein requires special translational cofactors to "read-through" a UGA-stop codon that specifies SEC incorporation at the active site of the enzyme. These factors include a selenocysteine incorporation sequence (SECIS) in the 3'-untranslated region of the GPx1 mRNA and cofactors involved in the biosynthesis and translational insertion of SEC. To monitor SEC incorporation, we used a reporter gene system that has a UGA codon within the protein-coding region of the luciferase mRNA. Addition of either the GPx1 or GPx3 SECIS element in the 3'-untranslated region of the luciferase gene stimulated read-through by 6-11-fold in selenium-replete cells; absence of selenium prevented translation. To alter cellular homocysteine production, we used methionine in the presence of aminopterin, a folate antagonist, co-administered with hypoxanthine and thymidine (HAT/Met). This treatment increased homocysteine levels in the media by 30% (p < 0.01) and decreased GPx1 enzyme activity by 45% (p = 0.0028). HAT/Met treatment decreased selenium-mediated read-through significantly (p < 0.001) in luciferase constructs containing the GPx1 or GPx3 SECIS element; most importantly, the suppression of selenium-dependent read-through was similar whether an SV40 promoter or the GPx1 promoter was used to drive transcription of the SECIS-containing constructs. Furthermore, HAT/Met had no effect on steady-state GPx1 mRNA levels but decreased GPx1 protein levels, suggesting that this effect is not transcriptionally mediated. These data support the conclusion that homocysteine decreases GPx1 activity by altering the translational mechanism essential for the synthesis of this selenocysteine-containing protein.
...
PMID:Homocysteine down-regulates cellular glutathione peroxidase (GPx1) by decreasing translation. 1573 34

Atherosclerotic risk is increased in diabetes partly because of increased plasma levels of the oxidized low-density lipoprotein and homocysteine, 2 independent and important cardiovascular disease (CVD) risk factors. Paraoxonase (PON) is a multifunctional antioxidant enzyme component of high-density lipoprotein (HDL), which can protect against low-density lipoprotein (LDL) oxidation. It also exhibits homocysteine thiolactonase (HCTL) activity that detoxifies homocysteine thiolactone, which can damage proteins by homocysteinylation of the lysine residues, thus leading to atherosclerosis. We conducted a cross-sectional study to correlate PON-1, HCTL activities, and the lag time of LDL oxidation in 15 healthy control subjects and in 55 subjects with type 2 diabetes mellitus with different degrees of CVD. Compared with healthy controls and diabetic subjects without evidence of overt CVD, we not only found 47% (P < .005) decrease in PON-1 activity, but also for the first time, 30% (P = .019) decrease in HCTL activity in subjects with a prior coronary artery bypass surgery. There was corresponding decreased effectiveness of HDLs from diabetic groups (with and without CVD) in protecting against LDL oxidation. Moreover, the PON-1 activity was significantly inversely correlated to the extent of intracoronary lesions determined at catheterization (ie, a high Gensini score). These decreases in PON-1 and HCTL activity were not due to any bias in preferential distribution of low-activity QQ homozygotes in the diabetic groups compared with the control group because QQ allele was equally distributed in all the experimental groups, whereas RR allele tended to increase in the diabetic subjects with coronary artery bypass surgery compared with the other groups. Therefore, clinical intervention to restore the impaired antiatherogenic activities of HDL should be considered an important goal in the treatment of persons with diabetes.
...
PMID:Inverse correlation of serum paraoxonase and homocysteine thiolactonase activities and antioxidant capacity of high-density lipoprotein with the severity of cardiovascular disease in persons with type 2 diabetes mellitus. 1691 39

The aims of this study were to investigate the effects of homocysteine (Hcy) on epididymal sperm characteristics, plasma testosterone level and biochemical changes related to oxidative stress and to examine the effects of melatonin (Mlt) or Vitamin E (VE) administration on these parameters in Hcy-treated male rats. In this study, 32 adult male albino rats of Wistar strain were used. The rats were randomly divided into four groups. The first group of rats received only Hcy (0.71 mg/kg/day) intraperitonially (ip) for 6 weeks. The second group of rats was given Hcy along with simultaneous administration of Mlt (1mg/kg/day) subcutaneously. The third group of rats received Hcy along with simultaneous administration of VE (125 mg/kg/day, ip). The fourth group of rats served as control during 6 weeks and was daily given 0.1 mL of physiological saline (NaCl, 0.9%) ip. While the plasma malondialdehyde level significantly (p<0.05) increased, the plasma superoxide dismutase, glutathione peroxidase and catalase activities significantly (p<0.05) decreased in Hcy-treated rats when compared to control rats. Furthermore, the epididymal sperm concentration, the percentage of progressive sperm motility and plasma testosterone level were significantly (p<0.05) lower in Hcy-treated rats than those of the control rats. The simultaneous administration of Mlt or VE to Hcy-treated animals impeded the decrease in the plasma antioxidant enzyme activities, testosterone level, the epididymal sperm concentration and motility. In conclusion, this study indicates that chronic administration of Hcy has the harmful effect on the epididymal sperm characteristics of male rats. The administration of Mlt or VE can prevent adverse effects of Hcy on the plasma antioxidant enzyme activities, testosterone level, epididymal sperm count and motility in male rats.
...
PMID:The protective effects of melatonin and Vitamin E on antioxidant enzyme activities and epididymal sperm characteristics of homocysteine treated male rats. 1717 11

Mildly elevated homocysteine levels (Hcy) increase the risk for atherothrombotic vascular disease in the coronary, cerebrovascular, and peripheral arterial circulations. The molecular mechanisms responsible for decreased bioavailability of endothelium-derived nitric oxide (NO) by Hcy involve an increase of vascular oxidant stress and inhibition of important antioxidant capacity. Glutathione peroxidase-1 (GPx-1), a selenocysteine-containing antioxidant enzyme, may be a key target of Hcy's deleterious actions, and several experimental and clinical studies have demonstrated a complex relationship between plasma total homocysteine (tHcy), GPx-1, and endothelial dysfunction. Hcy may promote endothelial dysfunction, in part by decreasing GPx-1 expression; however, there is evidence to suggest that overexpression of GPx-1 can compensate for these effects. This review summarizes the current knowledge of the metabolism of Hcy, the effects of hyperhomocysteinemia observed in in vitro and in vivo models that lead to endothelial dysfunction and the possible mechanisms for these actions, and the role of GPx-1 in the pathogenesis of Hcy-induced cardiovascular disease (CVD).
...
PMID:Homocysteine and glutathione peroxidase-1. 1782 68

Hyperhomocyteinaemia has been associated with pathological and stressful conditions and considered as a risk factor for cardiovascular diseases. Maternal protein restriction during late pregnancy and postnatal period is a stressful state to their offspring which is associated with disruption of various physiological processes. The objective of the current study was to evaluate the effects of maternal protein restriction during late pregnancy and early postnatal periods on systemic oxidative stress parameters and on homocysteine metabolism of their offspring. For this purpose, 12 female rats were divided into two groups: a control group (C) with free access to standard diet (20% protein) and a protein restricted group (PR) with free access to a low protein diet (7% protein) from the day 14 of pregnancy until day 14 after delivery. An increase of thiobarbituric acid-reactive substance levels (TBARS) in plasma (+40%, p < 0.01) and in liver (+37%, p < 0.001) with a concomitant decrease in the activities of catalase (CAT) and superoxide dismutase (SOD) observed in undernourished pups suggest the possibility of oxidative stress. Moreover, no significant changes in total glutathione levels (tGSH) were also observed to be associated with a significant decrease in homocysteine concentrations (-35%; p < 0.001). In their mothers, an alteration of antioxidant enzyme activities (CAT and SOD) and slight increase of TBARS levels were observed. Whereas homocysteine and tGSH levels were unchanged in comparison with those fed ad libitum. These results suggested that PR diet given to mothers during late pregnancy and early postnatal periods induced oxidative stress and hypohomocysteinaemia in their offspring.
...
PMID:Protein restriction in pregnant- and lactating rats-induced oxidative stress and hypohomocysteinaemia in their offspring. 1932 Sep 38

To investigate the effects of atorvastatin and cinnamon on serum lipid profile, oxidative stress, antioxidant capacity, hepatic enzymes activities, nitric oxide (NO) as well as homocysteine (Hcy) in hypercholesterolemic rats, 48 male albino rats, weighing 130-190 gm were divided into 2 groups, normal group fed on basal rat chow diet (n=12) and high cholesterol group (HCD) were fed on 1% cholesterol-enriched diet for 15 day (n=36). Hypercholesterolemic rats were divided into 3 subgroups (n=12 for each) fed the same diet and treated with atorvastatine (HCD+Atorvastatin) or cinnamon extract (HCD+cinnamon) or none treated (HCD) for 3&6 weeks. Serum triglycerides (TG), Total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), ALT, AST, NO, Hcy, hepatic reduced glutathione (GSH), Malondialdehyde (MDA) and antioxidant enzymes, Superoxide dismutase (SOD) and catalase activity were measured. Results showed that HCD increased significantly TG, TC, LDL-C, ALT, AST, Hcy and hepatic MDA, while lowered significantly antioxidant enzyme activities and NO levels. Atorvastatin therapy significantly increased HDL-C, NO and antioxidant activity while decreased LDL-C, MDA and Hcy concentrations. Serum TG, TC, LDL-C, ALT, AST and hepatic MDA levels were significantly lowered meanwhile, serum HDL, NO values and hepatic antioxidant activities were significantly, higher in cinnamon-treated than untreated group. These results indicate that lipid abnormalities, oxidative injury and hyperhomocystienemia were induced by HCD and this study recommend that administration of atorvastatine or cinnamon provided protection against the lipemic-oxidative disorder and act as hypocholesterolemic, hepatoprotective agent and improve cardiovascular function through modulation of oxidative stress, NO and Hcy.
...
PMID:Oxidative markers, nitric oxide and homocysteine alteration in hypercholesterolimic rats: role of atorvastatine and cinnamon. 1991 18

While the effects of chronic ethanol consumption on liver have been well studied and documented, its effect on the cardiovascular system is bimodal. Thus, moderate drinking in many population studies is related to lower prevalence of coronary artery disease (CAD). In contrast, heavy drinking correlates with higher prevalence of CAD. In several other studies of cardiovascular mortalities, abstainers and heavy drinkers are at higher risk than light or moderate drinkers. The composite of this disparate relation in several population studies of cardiovascular mortality has been a "U-" or "J-"shaped curve. Apart from its ability to eliminate cholesterol from the intima of the arteries by reverse cholesterol transport, another major mechanism by which HDL may have this cardioprotective property is by virtue of the ability of its component enzyme paraoxonase1 (PON1) to inhibit LDL oxidation and/or inactivate OxLDL. Therefore, PON1 plays a central role in the disposal of OxLDL and thus is antiatherogenic. Furthermore, PON1 is a multifunctional antioxidant enzyme that can also detoxify the homocysteine metabolite, homocysteine thiolactone (HTL), which can pathologically cause protein damage by homocysteinylation of the lysine residues, thereby leading to atherosclerosis. We demonstrated that moderate alcohol up regulates liver PON1 gene expression and serum activity, whereas heavy alcohol consumption had the opposite effects in both animal models and in humans. The increase in PON1 activity in light drinkers was not due to preferential distribution of high PON1 genotype in this group. It is well known that wine consumption in several countries shows a remarkable inverse correlation to local rates of CAD mortality. Significantly, apart from its alcohol content, red wine also has polyphenols such as quercetin and resveratrol that are also known to have cardioprotective effects. We have shown that quercetin also up regulates PON1 gene in rats and in human liver cells. The action of quercetin seems to be mediated via the active form of the nuclear lipogenic transcription factor, sterol-regulatory element-binding protein 2 (SREBP2) that is translocated from endoplasmic reticulum to the nucleus. However, the mechanism of action of ethanol-mediated up-regulation of PON1 gene remains to be elucidated. We conclude that both moderate ethanol and quercetin, the two major components of red wine, exhibit cardioprotective properties via the up-regulation of the antiatherogenic gene PON1.
...
PMID:Is alcohol beneficial or harmful for cardioprotection? 2001

1 2 3 Next >>