Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is the single leading cause of death and morbidity for Canadians. A universal feature of cardiovascular disease is dysfunction of the vascular endothelium, thus disrupting control of vasodilation, tissue perfusion, hemostasis, and thrombosis. Nitric oxide bioavailability, crucial for maintaining vascular endothelial health and function, depends on the processes controlling synthesis and destruction of nitric oxide as well as on the sensitivity of target tissue to nitric oxide. Evidence supports a major contribution by oxidative stress-induced destruction of nitric oxide to the endothelial dysfunction that accompanies a number of cardiovascular disease states including hypertension, diabetes, chronic heart failure, and atherosclerosis. Regular physical activity (exercise training) reduces cardiovascular disease risk. Numerous studies support the hypothesis that exercise training improves vascular endothelial function, especially when it has been impaired by preexisting risk factors. Evidence is emerging to support a role for improved nitric oxide bioavailability with training as a result of enhanced synthesis and reduced oxidative stress-mediated destruction. Molecular targets sensitive to the exercise training effect include the endothelial nitric oxide synthase and the antioxidant enzyme superoxide dismutase. However, many fundamental details of the cellular and molecular mechanisms linking exercise to altered molecular and functional endothelial phenotypes have yet to be discovered. The working hypothesis is that some of the cellular mechanisms contributing to endothelial dysfunction in cardiovascular disease can be targeted and reversed by signals associated with regular increases in physical activity. The capacity for exercise training to regulate vascular endothelial function, nitric oxide bioavailability, and oxidative stress is an example of how lifestyle can complement medicine and pharmacology in the prevention and management of cardiovascular disease.
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PMID:Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. 1625 83

High fructose-fed (HFF) rat model is known to develop the insulin-resistant syndrome with a very similar metabolic profile to the human X syndrome. Such metabolic modifications have been associated with a high incidence of cardiovascular disease. The role of free radical attack in diabetes mellitus and its cardiovascular complications have been abundantly documented. The present study examined the susceptibility to myocardial ischemic injury and the involvement of free radical attack and/or protection in the metabolic disorders of high FF rats. Rats were divided into two experimental groups that received diet for 4 weeks: a control group (C, n=28) receiving a standard diet and a HFF group (FF, n=28), in which 58% of the total carbohydrate was fructose. The euglycemic clamp technique was performed to assess insulin resistance. For the ischemia-reperfusion procedure, rat hearts were isolated and perfused at constant pressure before they were subjected to a 30-min occlusion of the left coronary artery followed by 120 mins of reperfusion. Hemodynamic parameters were measured throughout the protocol. Infarct-to-risk ratio (I/R) was assessed at the end of the protocol by 2,3,4-triphenyltetrazolium chloride staining and planimetric analysis. Lipid peroxidation, antioxidant enzyme activity, level of vitamin E, and trace element status were measured in blood samples from both groups. Rats of the FF group developed an insulin resistance indicated by the glucose infusion rate, which was decreased by 47%. Infarct size was significantly reduced in rats from the FF group (19.9% +/- 6.6%) compared to rats from the control group (34.6% +/- 4.9%), and cardiac functional recovery at reperfusion was improved in the FF group. Lipid peroxidation and oxidative stress were higher in the FF group, as indicated by higher malonedialdehyde level, whereas plasma vitamin E/triacylglycerol ratio was also enhanced in this group. This study indicates that fructose feeding affords protection against in vitro ischemia-reperfusion injury, potentially implicating vitamin E.
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PMID:Fructose-fed rat hearts are protected against ischemia-reperfusion injury. 1656 41

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.
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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

We have previously reported that estrogens up-regulate longevity-associated genes. As recent evidence has shown that estrogen replacement therapy is associated with an increased risk of cardiovascular disease, we have studied the effects of genistein, a soy isoflavone with a similar structure to estradiol, on the expression of antioxidant, longevity-related genes. MCF-7 cells (human mammary gland tumor cell line) were incubated for 48 h with 0.5 microM genistein, a concentration found in the plasma of populations consuming diets rich in soy protein. Peroxide levels were determined by fluorimetry, activation of extracellular-signal regulated kinase (ERK1/2), and nuclear factor kappaB (NFkappaB)-signaling pathways by Western blot analysis and ELISA, respectively, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Inhibition of basal peroxide levels in MCF-7 cells by genistein was prevented by pretreatment of cells with the estrogen receptor antagonist tamoxifen. Phosphorylation of extracellular regulated kinase (ERK)1/2 led to an activation of NFkappaB, as indicated by increased p50 subunit expression in nuclear extracts, and increased mRNA levels of the antioxidant enzyme manganese-superoxide dismutase (MnSOD). Inhibition of ERK1/2 abrogated genistein-mediated NFkappaB activation and elevated expression of MnSOD. Our molecular studies may provide a basis to determine the effects of genistein and other soy protein-derived products on longevity in both animals and the human population.
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PMID:Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: involvement of estrogen receptors, ERK1/2, and NFkappaB. 1696 88

Low ethanol intake is known to have a beneficial effect on cardiovascular disease. In cardiovascular disease, insulin resistance leads to altered glucose and lipid metabolism resulting in an increased production of aldehydes, including methylglyoxal. Aldehydes react non-enzymatically with sulfhydryl and amino groups of proteins forming advanced glycation end products (AGEs), altering protein structure and function. These alterations cause endothelial dysfunction with increased cytosolic free calcium, peripheral vascular resistance, and blood pressure. AGEs produce atherogenic effects including oxidative stress, platelet adhesion, inflammation, smooth muscle cell proliferation and modification of lipoproteins. Low ethanol intake attenuates hypertension and atherosclerosis but the mechanism of this effect is not clear. Ethanol at low concentrations is metabolized by low Km alcohol dehydrogenase and aldehyde dehydrogenase, both reactions resulting in the production of reduced nicotinamide adenine dinucleotide (NADH). This creates a reductive environment, decreasing oxidative stress and secondary production of aldehydes through lipid peroxidation. NADH may also increase the tissue levels of the antioxidants cysteine and glutathione, which bind aldehydes and stimulate methylglyoxal catabolism. Low ethanol improves insulin resistance, increases high-density lipoprotein and stimulates activity of the antioxidant enzyme, paraoxonase. In conclusion, we suggest that chronic low ethanol intake confers its beneficial effect mainly through its ability to increase antioxidant capacity and lower AGEs.
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PMID:Beneficial effect of low ethanol intake on the cardiovascular system: possible biochemical mechanisms. 1732 32

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).
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PMID:Homocysteine and glutathione peroxidase-1. 1782 68

Bilirubin is a potent antioxidant, however, uncertainty surrounds its physiological importance. Individuals with Gilbert's syndrome (GS) have increased circulating bilirubin and a reduced prevalence of cardiovascular disease (CVD). The aim of this study was to investigate mechanisms that may link bilirubin to protection from CVD seen in GS by examining markers of antioxidant and oxidative stress status and the susceptibility of serum to oxidation. Nine individuals with GS and twelve controls, matched for age, height and weight, were assessed for plasma antioxidant status, red blood cell antioxidant enzyme activities, plasma malondialdehyde, the susceptibility of serum to copper (Cu(2+)) induced oxidation and blood lipid profile. Individuals with GS had significantly elevated unconjugated bilirubin (GS: 26.0+/-6.4; control: 9.7+/-3.0 micromol/L; P<0.001), increased trolox equivalent antioxidant capacity (GS: 1.59+/-0.07; control: 1.52+/-0.07 mmol/L trolox Equ; P=0.035) and ferric reducing ability of plasma (GS: 1.09+/-0.16; control: 0.92+/-0.14 mmol/L Fe(2+) Equ; P=0.024). The lag phase of serum oxidation was significantly longer in the GS group (GS: 121.4+/-10.5; control: 106.8+/-14.6 min; P=0.020) and was positively correlated with the bilirubin concentration (r=0.451, P=0.040). A trend toward elevated HDL:LDL ratio was observed in GS (GS 0.96+/-0.31; control: 0.73+/-0.21; P=0.072). In summary, individuals with GS have an increased circulating antioxidant status and an improved resistance to serum oxidation which may partially explain their reduced prevalence of CVD.
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PMID:Improved resistance to serum oxidation in Gilbert's syndrome: a mechanism for cardiovascular protection. 1815 9

Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H2O2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.
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PMID:Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat. 1820 83

Decreased consumption of n-3 fatty acids (FA) and diets rich in animal proteins, saturated fats and n-6 vegetable oils are associated with a higher incidence of cardiovascular disease (CVD), certain malignancies and autoimmune disorders such as rheumatoid arthritis and Systemic Lupus Erythematosus (SLE), and renal disease. Recent studies show that reduced calorie intake and supplementation of diet with n-3 FA delays the onset of autoimmune renal disease, primarily, due to increased antioxidant enzyme activities, decreased NF-kappaB activation and decreased IL-1, IL-6 and TNF-alpha mRNA expression in the kidney tissue. Studies in rodents show that addition of n-3 FA and soy protein to diet affords protection against bone loss induced by ovariectomy in mice due to NF-kappaB expression and decreased activation of osteoclasts. Together, the available evidence show that increased daily intake of dietary n-3 FA decreases the severity of autoimmune disorders, lessens the chance of developing CVD, and protects against bone loss during post-menopause.
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PMID:Effects of n-3 fatty acids on autoimmunity and osteoporosis. 1850 95

Endothelial dysfunction underlies cardiovascular disease (CVD) in humans and is reported in animal models of developmental origins of such disease. We have investigated whether impaired antioxidant defences and NO generation underlie the genesis of endothelial dysfunction and operate as part of the normal processes of developmental plasticity regulating the induction of phenotype in the offspring. Female Wistar rats were fed either a control (C, 18% protein) or protein-restricted (PR, 9% protein) diet throughout pregnancy. Dams and pups were returned to standard laboratory chow post partum. In male offspring, PR resulted in a reduced endothelial responsiveness to acetylcholine (P < 0.05) in resistance arteries, with vascular remodelling evident from a reduction in smooth muscle content. mRNA expression of endothelial NO synthase (eNOS) was increased (P < 0.05) but there was no change in mRNA levels of manganese superoxide dismutase (MnSOD) or glutamate cysteine ligase (GCL) expression. Interestingly, expression of the antioxidant enzyme haem oxygenase-1 (HO-1) was reduced in the liver (P < 0.05). Female PR offspring also showed a reduced endothelial responsiveness but exhibited no changes in expression of eNOS, iNOS, soluble guanylate cyclase (sGC) or antioxidant genes. Thus, in this model of the developmental origins of CVD, the structure and function of resistance arteries in offspring is altered in complex ways which cannot simply be explained by attenuation in vascular eNOS or in antioxidant protection afforded by GCL or MnSOD. The dysfunction in male offspring may partially be counteracted by an up-regulation of eNOS expression; however, PR does lead to reduced HO-1 expression in these offspring, which may affect both their growth and vascular function. Our findings have established that PR induces significant phenotypic changes in male offspring that may be indicative of an adaptive response during development.
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PMID:Endothelial dysfunction and reduced antioxidant protection in an animal model of the developmental origins of cardiovascular disease. 1882 46


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