UNIPROT:P30044 - FACTA Search

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)

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

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

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

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

Toll-like receptor 4 (TLR4) and angiotensin II (AngII) induce vascular remodeling through the production of reactive oxygen species (ROS). AngII has also been shown to increase antioxidant enzyme extracellular superoxide dismutase (ecSOD). However, the roles of TLR4 in Ang II-induced ROS production, vascular remodeling and hypertension remain unknown. Mice lacking TLR4 function showed significant inhibition of vascular remodeling in response to chronic AngII infusion, with no impact on blood pressure. The increases in ROS level and NADPH oxidase activity in response to AngII infusion were markedly blunted in TLR4-deficient mice. Similar effects were observed in wild-type (WT) mice treated with a sub-depressor dose of the AT1 receptor antagonist irbesartan, which had no effects on TLR4-deficient mice. Intriguingly, the AngII infusion-induced increases in ecSOD activity and expression were rather enhanced in TLR4-deficient mice compared with WT mice, whereas the expression of the proinflammatory chemokine MCP-1 was decreased. Importantly, AngII-induced vascular remodeling was positively correlated with NADPH oxidase activity, ROS levels and MCP-1 expression levels. Notably, chronic norepinephrine infusion, which elevates blood pressure without increasing ROS production, did not induce significant vascular remodeling in WT mice. Taken together, these findings suggest that ROS elevation is required for accelerating vascular remodeling but not for hypertensive effects in this model. We demonstrated that TLR4 plays a pivotal role in regulating AngII-induced vascular ROS levels by inhibiting the expression and activity of the antioxidant enzyme ecSOD, as well as by activating NADPH oxidase, which enhances inflammation to facilitate the progression of vascular remodeling.
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PMID:TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the roles of extracellular SOD and NADPH oxidase. 2599 4

Angiotensin II (Ang II), as a crucial factor of endothelial dysfunction, participates in endothelial oxidative damage and inflammation, which is present in all cardiovascular disease (CVD). Celastrol, extracted from Trypterygiun wilfordii Hook F. ("Thunder of God Vine"), is a natural compound with antioxidant and anti-inflammatory activities. In this study, the protective effects of celastrol on human umbilical vein endothelial cell (HUVEC) injury induced by Ang II were observed and its mechanisms were elucidated. Compared with the control group, Ang II significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, enhanced reactive oxygen species levels and proinflammatory cytokines, decreased antioxidant enzyme activities, and suppressed cellular viability and promoted cell apoptosis. It accomplished this via inhibition of the nuclear factor erythroid 2-related factor 2 (Nrf2), increasing the expression levels of Nox2 and AngII type 1 receptor (AT₁ receptor), and inducing the phosphorylation of extracellular signal regulated kinase (ERK1/2). In contrast, celastrol effectively suppressed reactive oxygen species generation, improved endothelial cell activity, and ameliorated Ang II-mediated HUVEC injury through activation of Nrf2, inhibition of Nox2/AT₁ receptor expression, and upregulated phosphorylation of ERK1/2. After treatment with brusatol, a specific inhibitor of Nrf2, the protective effects of celastrol on Ang II-induced damage in HUVECs were remarkably alleviated. Taken together, celastrol-induced activation of Nrf2 and inhibition of NADPH oxidase activity were critical for the inhibition of Ang II-mediated endothelial dysfunction, and demonstrated the potential application of celastrol in CVD therapy.
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PMID:Celastrol attenuates angiotensin II mediated human umbilical vein endothelial cells damage through activation of Nrf2/ERK1/2/Nox2 signal pathway. 2811 74

The crude protein hydrolysates of wild hazel have good immunoregulation and antioxidation effects. However, the components responsible for their antioxidation effect remain unknown. In this study, six antioxidative peptides (EW, DWDPK, ADGF, SGAF, ETTL, and AGGF) were tested for their protective effects on oxidative stress injury in human umbilical vein endothelial cells (HUVECs). The results demonstrated that the six peptides are nontoxic and have a protective effect on oxidative stress injury induced by Ang II. Three peptides (EW, ADGF, and DWDPK) inhibited the morphological changes, downregulated the content of lactate dehydrogenase and malondialdehyde, upregulated the activity of antioxidant enzymes catalase, total superoxide dismutase and glutathione peroxidase, and scavenged reactive oxygen species (ROS) in HUVECs. Quantitative reverse transcriptive polymerase chain reaction and western blot assays indicated that these three peptides regulated NADPH oxidase activity and ROS production by reducing NOX4 and p22phox levels. Overall, they have a significant protective effect against oxidative stress injury and have potential application in developing new functional foods. PRACTICAL APPLICATIONS: Corylus heterophylla Fisch is a good quality wild hazel distributed in Northeast China. Wild hazelnut of the species C. heterophylla Fisch was selected as experimental object and has high nutritive values and have abundant proteins (20%-30%), fats (40%-50%), carbohydrates (13%-24%), dietary fibers (8.2%-9.6%), vitamins, and micronutrients. Our results indicate that hazelnut peptides (EW, ADGF, and DWDPK) can ensure normal growth of cells by protecting important antioxidant enzyme systems, by enhancing antioxidant defense, by directly affecting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and by reducing intracellular reactive oxygen species (ROS) production in HUVECs, indicating that the three antioxidative peptides have a protective effect against Ang II-induced oxidative stress injury. Therefore, the antioxidative peptides from C. heterophylla Fisch may be a promising candidate for functional food ingredients and/or pharmaceuticals.
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PMID:Protective role of hazelnut peptides on oxidative stress injury in human umbilical vein endothelial cells. 3135 65

We investigated the mechanism by which ACE2 (angiotensin-converting enzyme 2) overexpression alters neurohumoral outflow and central oxidative stress. Nrf2 (nuclear factor [erythroid-derived 2]-like 2) is a master antioxidant transcription factor that regulates cytoprotective and antioxidant genes. We hypothesized that upregulation of central ACE2 inhibits the pressor response to Ang II (angiotensin II) by reducing reactive oxygen species through a Nrf2/antioxidant enzyme-mediated mechanism in the rostral ventrolateral medulla. Synapsin human Angiotensin Converting Enzyme 2 positive (SynhACE2^+/+) mice and their littermate controls synhACE2^-/- were used to evaluate the consequence of intracerebroventricular infusion of Ang II. In control mice, Ang II infusion evoked a significant increase in blood pressure and norepinephrine excretion, along with polydipsia and polyuria. The pressor effect of central Ang II was completely blocked in synhACE2^+/+ mice. Polydipsia, norepinephrine excretion, and markers of oxidative stress in response to central Ang II were also reduced in synhACE2^+/+ mice. The MasR (Mas receptor) agonist Ang 1-7 and blocker A779 had no effects on blood pressure. synhACE2^+/+ mice showed enhanced expression of Nrf2 in the rostral ventrolateral medulla which was blunted following Ang II infusion. Ang II evoked nuclear translocation of Nrf2 in cultured Neuro 2A (N2A) cells. In synhACE2^-/- mice, the central Ang II pressor response was attenuated by simultaneous intracerebroventricular infusion of the Nrf2 activator sulforaphane; blood pressure was enhanced by knockdown of Nrf2 in the rostral ventrolateral medulla in Nrf2 floxed (Nrf2^f/f) mice. These data suggest that the hypertensive effects of intracerebroventricular Ang II are attenuated by selective overexpression of brain synhACE2 and may be mediated by Nrf2-upregulated antioxidant enzymes in the rostral ventrolateral medulla.
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PMID:Overexpression of Central ACE2 (Angiotensin-Converting Enzyme 2) Attenuates the Pressor Response to Chronic Central Infusion of Ang II (Angiotensin II): A Potential Role for Nrf2 (Nuclear Factor [Erythroid-Derived 2]-Like 2). 3289 18

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