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)

Angiotensin II administration to rats during 6 weeks causes decreased activity of catalase and glutathione peroxidase in renal cortex. Rats show mild hypertension, subclinical signs of renal injury, increased glomerular expression of desmin, glomerular and interstitial expression of alpha-smooth muscle actin and an increased number of ED-1-positive cells in glomeruli. An inverse correlation exists between catalase activity and glomerular alpha-smooth muscle actin expression and between glutathione peroxidase activity and glomerular desmin expression. The decrease of antioxidant enzyme activity, early after angiotensin II administration, might be an important initiating factor in the complex process leading eventually to renal sclerosis by reduction of reactive oxygen intermediate breakdown. The significant relationship between markers of sclerosis and some antioxidant enzyme activities suggests either a causative link or a common triggering factor.
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PMID:Angiotensin II administration causes enhanced expression of glomerulosclerosis-related markers and decreased renal antioxidant enzyme activities in rats. 1115 Aug 61

This study was aimed to study the angiotensin II (Ang II)-induced antioxidant changes in the kidney of borderline-hypertensive rats (BHR). We measured renal antioxidant enzyme activities, and glutathione (GSH) contents and lipid peroxide levels in relation to the age of subjects. In the antioxidant enzyme assays, consistent changes were not observed in relation to age. However, in the assay for reduced GSH, nonenzymatic antioxidant, contents of adult and aged rats were much greater than those of weanling rats. Subcutaneous injection of pressor dose of human Ang II (200 microg/kg over 90 min) significantly reduced enzymatic activities in the weanling (4-week-aged) and adult (10-week-aged) BHR. However, in the relatively aged (16-week-aged) rats, Ang II did not alter enzymatic activities. Renal GSH contents of aged BHR, were highly increased by Ang II. Renal lipid peroxide levels of weanling and adult BHR were increased by Ang II, but decreased in the aged rats. However, these characteristic changes of renal antioxidant due to Ang II of the BHR could not be observed in the age-matched control, Wistar-Kyoto rats (WKR). From these results, it can be concluded that impacts of oxidative stress on the kidney of BHR may be greater in the young rats.
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PMID:Effects of angiotensin II on the renal antioxidant activities of borderline hypertensive rats. 1152 11

Hypertension caused by angiotensin II is characterized by an increase in tissue oxidant stress as evidenced by increased quantities of reactive oxygen and nitrogen species. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme that is inactivated in conditions of oxidant stress by reacting with peroxynitrite to form 3-nitrotyrosine in its active site. The increase in 3-nitrotyrosine content in MnSOD in the kidney of angiotensin II-infused rats was assessed in this study by immunohistochemistry, Western blotting, immunoprecipitation, and HPLC with UV detection (HPLC-UV). MnSOD activity decreased approximately 50% in angiotensin II-infused rat kidneys (24 +/- 4.6 vs. 11 +/- 5.2 U/mg) without a change in protein expression. Immunohistochemical staining showed 3-nitrotyrosine predominantly in distal tubules and collecting duct cells in the angiotensin II-infused rat kidneys. By two-photon microscopy, 3-nitrotyrosine colocalized with MnSOD. Total 3-nitrotyrosine content in kidney homogenates was increased in angiotensin II-infused rat kidney [3.2 +/- 1.9 (sham treated) vs. 9.5 +/- 2.3 ng/mg protein by HPLC-UV detection]. With tracer amounts of tyrosine-nitrated recombinant MnSOD, the most sensitive technique to detect tyrosine nitration of MnSOD was immunoprecipitation from tissue with anti-MnSOD antibody, followed by detection of 3-nitrotyrosine by Western blotting or HPLC. By HPLC, 3-nitrotyrosine content of kidney MnSOD increased 13-fold after angiotensin II infusion, representing an increase from approximately one-twentieth to one-fifth of the total 3-nitrotyrosine content in sham-treated and angiotensin II-infused rat kidney, respectively. Angiotensin II-induced hypertension is accompanied by increased tyrosine nitration of MnSOD, which, because it inactivates the enzyme, may contribute to increased oxidant stress in the kidney.
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PMID:Quantitative assessment of tyrosine nitration of manganese superoxide dismutase in angiotensin II-infused rat kidney. 1279 89

Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2'-7' dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. A three times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy.
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PMID:Changes in oxidative balance in rat pericytes exposed to diabetic conditions. 1509 Feb 67

The aim of this study was to provide new insights into the role of angiotensin II and arterial pressure in the regulation of antioxidant enzyme activities in a renovascular model of cardiac hypertrophy. For this purpose, aortic coarcted rats were treated with losartan or minoxidil for 7 days. Angiotensin II induced cardiac hypertrophy and oxidative stress via Nox4, p22(phox) and p47(phox), which are components of the NAD(P)H oxidase. Antioxidant enzymes were regulated by arterial pressure and were not implicated in cardiac hypertrophy. Heme oxygenase-1, the rate-limiting enzyme in heme catabolism, behaved as a catalase and glutathione peroxidase, and is regulated by arterial pressure. In summary, the present report indicates that cardiac hypertrophy, induced by renovascular hypertension, depends on angiotensin II through reactive oxygen species and is not prevented by the action of antioxidant enzymes.
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PMID:Angiotensin II regulates cardiac hypertrophy via oxidative stress but not antioxidant enzyme activities in experimental renovascular hypertension. 1836 53

Angiotensin II (Ang II) is a peptide hormone able to elicit a strong production of reactive oxygen species by human neutrophils. In this work, we have addressed whether expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, becomes altered in these cells upon Ang II treatment or under hypertension conditions. In neutrophils from healthy and hypertensive subjects, induction of HO-1 mRNA and protein expression with a parallel increase in enzyme activity took place upon treatment with 15-deoxy-Delta12,14-PGJ2 (15dPGJ2). However, Ang II prevented HO-1 synthesis by normal neutrophils in vitro, and HO-1 expression was depressed in neutrophils from hypertensive patients in comparison with cells from healthy subjects. In addition, Ang II treatment led to a reduced HO-1 enzyme activity to levels similar to those found in neutrophils from hypertensive patients. NO donors reversed the inhibition of 15dPGJ2-dependent HO-1 expression in neutrophils from hypertensive patients, and conversely, inhibition of inducible NO synthase (NOS2) activity counteracted the stimulatory effect of 15dPGJ2 on HO-1 expression in normal human neutrophils. Moreover, Ang II canceled 15dPGJ2-dependent induction of NOS2 mRNA synthesis. Present findings indicate that down-regulation of HO-1 expression in neutrophils from hypertensive subjects is likely exerted through the inhibition of NOS2 expression. Additionally, they underscore the potential usefulness of NO donors as new, therapeutic agents against hypertension.
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PMID:Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils. 1851 25

Reactive oxygen species increase in the cardiovascular system during hypertension and in response to angiotensin II. Because mitochondria contribute to reactive oxygen species generation, we sought to investigate the role of thioredoxin 2, a mitochondria-specific antioxidant enzyme. Mice were created with overexpression of human thioredoxin 2 (Tg(hTrx2) mice) and backcrossed to C57BL/6J mice for > or =6 generations. Twelve-week-old male Tg(hTrx2) or littermate wild-type mice were made hypertensive by infusion of angiotensin II (400 ng/kg per minute) for 14 days using osmotic minipumps. Systolic arterial blood pressure was not different between Tg(hTrx2) and wild-type animals under baseline conditions (101+/-1 respective 102+/-1 mm Hg). The angiotensin II-induced hypertension in wild-type mice (145+/-2 mm Hg) was significantly attenuated in Tg(hTrx2) mice (124+/-1 mm Hg; P<0.001). Aortic endothelium-dependent relaxation was significantly reduced in wild-type mice after angiotensin II infusion but nearly unchanged in transgenic mice. Elevated vascular superoxide and hydrogen peroxide levels, as well as expression of NADPH oxidase subunits in response to angiotensin II infusion, were significantly attenuated in Tg(hTrx2) mice. Mitochondrial superoxide anion levels were augmented after angiotensin II infusion in wild-type mice, and this was blunted in Tg(hTrx2) mice. Angiotensin II infusion significantly increased myocardial superoxide formation, heart weight, and cardiomyocyte size in wild-type but not in Tg(hTrx2) mice. These data indicate a major role for mitochondrial thioredoxin 2 in the development of cardiovascular alterations and hypertension during chronic angiotensin II infusion. Thioredoxin 2 may represent an important therapeutic target for the prevention and treatment of hypertension and oxidative stress.
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PMID:Attenuation of angiotensin II-induced vascular dysfunction and hypertension by overexpression of Thioredoxin 2. 1950 95

Angiotensin II (Ang II) plays a profound regulatory effect on NADPH oxidase and the functional features of vascular adventitial fibroblasts, but its role in antioxidant enzyme defense remains unclear. This study investigated the effect of Ang II on expressions and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in adventitial fibroblasts and the possible mechanism involved. Ang II decreased the expression and activity of CAT in a dose- and time-dependent manner, but not that of SOD and GPx. The effects were abolished by the angiotensin II type 1 receptor (AT1R) blocker losartan and AT1R small-interfering RNA (siRNA). Incubation with polyethylene glycol-CAT prevented the Ang II-induced effects on reactive oxygen species (ROS) generation and myofibroblast differentiation. Moreover, Ang II rapidly induced phosphorylation of ERK1/2, which was reversed by losartan and AT1R siRNA. Pharmacological blockade of ERK1/2 improved Ang II-induced decrease in CAT protein expression. These in vitro results indicate that Ang II induces ERK1/2 activation, contributing to the downregulation of CAT as well as promoting oxidative stress and adventitial fibroblast phenotypic differentiation in an AT1R-mediated manner.
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PMID:Angiotensin II downregulates catalase expression and activity in vascular adventitial fibroblasts through an AT1R/ERK1/2-dependent pathway. 2166 Apr 62

Intracellular reactive oxygen species (ROS) are derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Angiotensin II (Ang II) can cause endothelial dysfunction by promoting intracellular ROS generation. Safflor yellow B (SYB) effectively inhibits ROS generation by upregulating Bcl-2 expression. In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels of target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of AT1R and p22(phox), increased NADPH oxidase activity, and an increased ratio of Bax/Bcl-2, leading to decreases in antioxidant enzyme activities, which were further strengthened after blocking Bcl-2. Compared to Ang II treatment alone, co-treatment with SYB significantly reversed HUVEC injury. Taken together, these results demonstrate that SYB could significantly protect endothelial cells from Ang II-induced cell damage, and that it does so by upregulating Bcl-2 expression and inhibiting ROS generation.
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PMID:Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22(phox) expression. 2399 55

As a novel gasotransmitter, hydrogen sulfide (H(2)S) has vasodilating and antihypertensive effects in cardiovascular system. Thus, we hypothesized that H(2)S might have beneficial effects on thoracic endothelial function in two-kidney one-clip (2K1C) rats, a model of renovascular hypertension. Sodium hydrosulfide (NaHS, 56 micromol/kg/day) was administrated intra-peritoneally from the third day after the 2K1C operation. Along with the development of hypertension, the systolic blood pressure (SBP) was measured before the operation and each week thereafter. The oxidative stress was determined by measurement of malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity and protein expression of oxidative stress-related proteins (AT(1)R, NADPH oxidase subunits). Acetylcholine (ACh)-induced vasorelaxation and angiotensin II (Ang II)-induced vasocontraction were performed on isolated thoracic aorta. The SBP was significantly increased from the first week after operation, and was lowered by NaHS. NaHS supplementation ameliorated endothelial dysfunction. The protein expression of oxidative stress-related proteins were downregulated, while SOD activity upregulated. In conclusion, improvement of endothelial function is involved in the antihypertensive mechanism of H(2)S. The protective effect of H(2)S is attributable to suppression of vascular oxidative stress that involves inhibition of Ang II-AT(1)R action, downregulation of oxidases, as well as upregulation of antioxidant enzyme.
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PMID:Hydrogen sulfide improves the endothelial dysfunction in renovascular hypertensive rats. 2580 97


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