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)

Heme oxygenase (HO)-1, involved in the heme degradation process, is an important antioxidant enzyme. The induction of HO-1 gene expression, in response to diverse oxidative stimuli, represents a critical event in adaptive cellular response. Experimental models of various diseases, including acute inflammation, atherosclerosis, degenerative diseases, and carcinogenesis, have demonstrated that the induction of HO-1 can prevent or mitigate the symptoms associated with these ailments. Recent progress in our understanding of cellular signaling networks as critical modulators of gene transcription sheds light on the molecular basis of HO-1 gene expression. A panel of redox-sensitive transcription factors such as activator protein-1, nuclear factor- kappaB, and nuclear factor E2-related factor-2, and some of the upstream kinases have been identified as regulators of HO-1 gene induction. The scope of this review is limited to focus on molecular mechanisms underlying HO-1 expression and the significance of targeted induction of HO-1 as a strategy to achieve chemoprevention and chemoprotection.
 ...
PMID:Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemoprotection. 1635 30

Oxidative stress is thought to contribute to the initiation and progression of atherosclerosis. As glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that detoxifies lipid hydroperoxides, we tested the impact of Gpx1 deficiency on atherosclerotic processes and antioxidant enzyme expression in mice fed a high-fat diet (HFD). After 12 weeks of HFD, atherosclerotic lesions at the aortic sinus were of similar size in control and Gpx1-deficient mice. However, after 20 weeks of HFD, lesion size increased further in control but not in Gpx1-deficient mice, even though plasma and aortic wall markers of oxidative damage did not differ between groups. In control mice, the expression of Gpx1 increased and that of Gpx3 decreased at the aortic sinus after 20 weeks of HFD, with no change in the expression of Gpx2, Gpx4, catalase, peroxiredoxin-6, glutaredoxin-1 and -2, or thioredoxin-1 and -2. By comparison, in Gpx1-deficient mice, the expression of antioxidant genes was unaltered except for a decrease in glutaredoxin-1 and an increase in glutaredoxin-2. These changes were associated with increased expression of the proinflammatory marker monocyte chemoattractant protein-1 in control mice but not in Gpx1-deficient mice. In summary, a specific deficiency in Gpx1 was not accompanied by an increase in markers of oxidative damage or increased atherosclerosis in a murine model of HFD-induced atherogenesis.
 ...
PMID:Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet. 1650 38

Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, -108C/T). The mean blood lead level (+/-SD) of this cohort was 27.1+/-15 microg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p<0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele.
 ...
PMID:Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes. 1763 95

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

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis, and an increased susceptibility of plasma lipids and lipoproteins to oxidation could at least in part promote atherogenesis. The objective of this study was to identify the effects of anticardiolipin antibody (aCL) and disease activity on oxidative and antioxidative status in patients with SLE. In this study, patients in SLE/aCL+ group and in SLE disease activity index >3 group had significantly higher thiobarbituric acid reactive substance (TBARS) levels, titers of autoantibodies against oxidized low-density lipoprotein (ox-LDL), and glutathione peroxidase activity than that of healthy controls. However, only TBARS and titers of autoantibodies against ox-LDL but not antioxidant enzyme activities were significantly different between SLE subgroups. Thus, enhanced oxidative status but not corresponding elevated antioxidative status by the presence of aCL and active disease activity make potent antioxidant therapy valuable for these SLE patients in preventing oxidative damage.
 ...
PMID:Enhanced oxidative status but not corresponding elevated antioxidative status by anticardiolipin antibody and disease activity in patients with systemic lupus erythematosus. 1702 58

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.
 ...
PMID:Beneficial effect of low ethanol intake on the cardiovascular system: possible biochemical mechanisms. 1732 32

Oxidative stress, increased lipid peroxidation, and impaired function of antioxidant system may contribute to the accelerated development of atherosclerosis in chronic renal failure patients during renal replacement therapy. The aim of the study was to investigate the influence of oral vitamin E (400 mg/day) in 14 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) and effects of the vitamin E-coated dialyzer in 14 haemodialysis patients on several antioxidant biochemical parameters. Six-week treatment with oral vitamin E in CAPD patients and three-month treatment using vitamin E-coated dialyzer in haemodialysis patients led to the significant decrease of plasma malondialdehyde, to the increase of plasma vitamin E and to the increase of erythrocyte vitamin E in haemodialysis patients. No significant changes of erythrocyte antioxidant enzyme--superoxide dismutase, glutathione peroxidase and catalase were found during the both types of antioxidant therapy. At the end of the third month of haemodialysis study the significant increase of erythrocyte glutathione in haemodialysis patients was found, but that value was significantly lower as normal range. Six-week interruption of the administration of oral vitamin E in CAPD patients led to the significant decrease of erythrocyte superoxide dismutase and plasma vitamin E. Ten-week interruption of the use of vitamin E-coated dialyzer led to the significant increase of plasma malondialdehyde and to the decrease of plasma and erythrocyte vitamin E in haemodialysis patients, near to the values at the beginning of the study. Our study confirmed the beneficial effect of oral administration of vitamin E and the use of vitamin E-coated dialyzer against oxidative stress in CAPD and haemodialysis patients.
 ...
PMID:Antioxidant therapy by oral vitamin E and vitamin E-coated dialyzer in CAPD and haemodialysis patients. 1738 8

Hypothyroidism enhances the progression of atherogenesis. Furthermore, dyslipidemia, hypertension, and obesity are known risk factors for atherosclerosis. Oxidative stress is implicated in the pathogenesis of cardiovascular diseases. However, there are contradicting reports on the existence of oxidative stress in hypothyroidism. Thus, the aim of the study is to evaluate the presence of oxidative stress in hypothyroidism and, if so, its possible association with various coronary lipid risk factors. The present study was carried out in a group of 27 freshly diagnosed normotensive primary hypothyroid female patients in comparison with healthy subjects. Their body mass index (BMI), serum thyroid profile, lipid profile, glucose, protein carbonylation, thiobarbituric acid reactive substances (TBARS), and blood antioxidant enzyme levels were estimated. The TBARS and protein carbonylation were significantly higher in cases compared with those in controls. Reduced glutathione was lower and glutathione peroxidase was higher in the test group compared with those in controls. Various lipid risk factors for coronary artery disease were significantly higher among the hypothyroid women in comparison with those in controls. The level of TBARS correlated significantly with various lipid risk factors among the hypothyroid women even after correcting the effect of BMI. However, no significant associations were observed between BMI and these risk factors when the effect of TBARS was nullified. In hypothyroidism, the coronary lipid risk factors seem to be more associated with lipid peroxidation than BMI. In conclusion, the present study indicates the presence of oxidative stress in hypothyroid patients and its association with atherogenic dyslipidemia, which is independent of BMI.
 ...
PMID:Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index. 1788 44

Altered activities of high-density lipoprotein (HDL)-associated antioxidant enzyme paraoxonase 1 (PON1) and lipid transfer proteins, for example, cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT), participating in lipoprotein remodeling seem to play important roles in obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum leptin levels have been demonstrated. However, the relationship of leptin with CETP and LCAT in humans is less clear. Our aims were to investigate whether the elevated leptin level is (a) an independent predictor of low PON1 and (b) associated with alterations of CETP and LCAT activities. Seventy-four white subjects forming 3 age- and sex-matched groups were included into the study (groups 1 and 2: nondiabetic obese patients, n = 25 with body mass index [BMI] 28-39.9 kg/m2 and n = 25 with BMI >or=40 kg/m2, respectively; and group 3: 24 healthy, normal-weight control subjects). Paraoxonase 1 correlated inversely with BMI (r = -0.39, P < .01), waist circumferences (r = -0.42, P < .001), and leptin concentrations (r = -0.38, P < .001). However, in a multiple regression model, neither these variables nor others, for example, age, sex, blood pressure, insulin resistance (in homeostasis model assessment of insulin resistance [HOMA-IR]), HDL cholesterol, low-density lipoprotein cholesterol, or lipid peroxidation (measured as thiobarbituric acid reactive substances), proved to be independent predictors of PON1. Lecithin cholesterol acyltransferase correlated negatively with BMI (r = -0.40, P < .01), waist circumferences (r = -0.42, P < .001), and leptin levels (r = -0.40, P < .01). During multiple regression analyses, BMI was an independent predictor of LCAT after adjustments for age, sex, HOMA-IR, and HDL cholesterol. However, this was replaced by leptin and HOMA-IR when leptin was also included into the model. The CETP activities correlated with HOMA-IR (r = 0.33, P < .01), thiobarbituric acid reactive substances (r = 0.45, P < .001), and leptin (r = 0.36, P < .01) levels in univariate but not in multivariate models. Elevated leptin level is an independent predictor of low LCAT, but not PON1, activity. In a population with a wide range of BMI, LCAT correlates inversely with obesity and CETP directly with insulin resistance.
 ...
PMID:Relationship of endogenous hyperleptinemia to serum paraoxonase 1, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase in obese individuals. 1795 Jan 6

Metabolic syndrome is considered a hyperinsulinemic and inflammatory state closely associated to endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. The main objective of the present study was to determine whether leukocitary and soluble cell adhesion molecules were altered in patients with metabolic syndrome in comparison with control subjects. Cell adhesion molecules, mainly of leukocitary location, have been not previously evaluated in specifically designed cross-sectional studies involving male patients with metabolic syndrome. Moreover, other circulating markers of different candidate atherogenic risk parameters were also studied and the potential existence of a progressive relation between the number of metabolic syndrome components and the above mentioned biomarkers was analyzed. Thirty one male patients with metabolic syndrome (ATPIII definition) and 56 male control subjects were studied. We evaluated different markers of insulin resistance, inflammation and atherosclerosis, as well as protective factors. Patients with metabolic syndrome showed (a) hypoadiponectinemia (4551 +/- 2302 ng/ml vs. 5865 +/- 2548 ng/ml, respectively; p<0.05), (b) an atherogenic lipid and lipoprotein profile, (c) altered HDL chemical composition accompanied by higher cholesteryl ester-triglyceride interchange carried out by CETP, (d) diminished Lp-PLA(2) activity (6.5 +/- 1.9 vs. 7.3 +/- 2.2, p<0.05, respectively), antioxidant enzyme related with LDL oxidation, which was positively associated with QUICKI and negatively with VCAM-1 and lymphocyte CD18, and (e) high soluble (VCAM-1: 17 +/-5 vs. 13 +/- 4 ng/ml, respectively; p<0.0005) and leukocyte adhesion molecule expression (monocyte CD54: 52 +/- 15 vs. 45 +/-12 arbitrary units, respectively; p<0.0005; and lymphocyte CD49d: 312 +/- 56 vs. 284 +/- 64 arbitrary units, respectively; p < 0.05). The increment in leukocyte and soluble cell adhesion molecules, crucial for leukocyte interaction with the endothelium and migration into the artery wall, in combination with the other disorders described above reinforce the presence of a clinical status with high propensity to type 2 diabetes and atherosclerotic cardiovascular disease.
Atherosclerosis 2008 Aug
PMID:Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with metabolic syndrome. 1809 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>