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)

We investigated the effects of lotus seedpod proanthocyanidins (LSPC) administration by oral gavage for 3 months on body weight, learning and memory deficits using Y-maze test, oxidative stress and antioxidative enzyme activity in brain and serum of the senescence-accelerated mice (SAMP8) and the senescence-resistant mice (SAMR1). Mice of each group were weighed weekly. Brain was obtained from SAMP8 and SAMR1 (the control mouse for SAMP8) at 6 months of age and serum was available from SAMP8 and SAMR1 at 3, 4, 5 and 6 months of age. The results of body weight showed that 90mg/kg LSPC administration significantly increased body weight at 5.5 and 6 months of age in SAMP8 when compared with control SAMP8 of the same age. Y-maze test indicated that learning and memory abilities of mice were deteriorated significantly at 6 months of age in SAMP8 compared with age-matched SAMR1, but were remarkably improved after LSPC (60, 90, 120mg/kg body weight) administration beginning at 3 months of ages. Malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) exhibited significant increases mostly at 5 and 6 months of age in SAMP8. Glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities decreased significantly mostly at 5 and 6 months of age in SAMP8. LSPC (60, 90, 120mg/kg body weight) administration beginning at 3 months of ages decreased MDA, NO content and lowered NOS activity in the brain and serum of SAMP8. Furthermore, LSPC significantly increased GSH level and augmented GPx, SOD activity in the brain and serum of SAMP8. These results suggest that an age-related increase in brain tissue vulnerability to oxidation and deterioration in learning and memory abilities in SAM that can be modified by LSPC, most likely through the ability of LSPC to scavenge oxygen free radicals and to stimulate antioxidant enzyme activity.
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PMID:Ameliorative effects of lotus seedpod proanthocyanidins on cognitive deficits and oxidative damage in senescence-accelerated mice. 1865 48

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

We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO2 and NO3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-beta, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-beta1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-beta1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-beta expression.
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PMID:Renoprotective mechanisms of soy protein intake in the obese Zucker rat. 1881 16

Oxidative stress mediated by hyperglycaemia-induced generation of reactive oxygen species (ROS) contributes significantly to the development and progression of diabetes and related vascular complications. NAD(P)H oxidase has been implicated as the major source of ROS generation in the vasculature in response to high glucose and advanced glycation end-products. Sustained activation of NAD(P)H oxidase in diabetes may diminish intracellular levels of NADPH, an essential cofactor for endothelial NO synthase (eNOS) and several antioxidant systems. Recent evidence suggests that basal ROS production via NAD(P)H oxidase may upregulate antioxidant enzyme defenses via redox signalling. Thus, NAD(P)H oxidase may serve as a double-edged sword, with transient activation providing a feedback defense against excessive ROS generation through the activation of receptor tyrosine kinases and the redox-sensitive Nrf2-Keap1 signalling pathway. Overproduction of ROS leads to eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant defenses owing to depletion of intracellular NADPH. Given the largely negative outcome of antioxidant therapy in the treatment of diabetic complications, targeting the redox-sensitive transcription factor Nfr2 may provide an effective strategy to restore antioxidant defenses in diabetes.
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PMID:Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling. 1917 52

Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5-100 microg/ml) for 2 h and then incubated with oxLDL (150 microg/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu,Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by GbE (P < 0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction.
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PMID:Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells. 1922 86

Rosemary leaves, "Rosmarinus officinalis", possess a variety of antioxidant, anti-tumoral and anti-inflammatory bioactivities. We hypothesized that rosemary extract could enhance antioxidant defenses and improve antioxidant status in aged rats. This work evaluates whether supplementing their diet with supercritical fluid (SFE) rosemary extract containing 20% antioxidant carnosic acid (CA) reduces oxidative stress in aged rats. Aged Wistar rats (20 months old) were included in the study. Rats were fed for 12 weeks with a standard kibble (80%) supplemented with turkey breast (20%) containing none or one of two different SFE rosemary concentrations (0.2% and 0.02%). After sacrifice, tissue samples were collected from heart and brain (cortex and hippocampus). Enzyme activities of catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and nitric oxide synthase (NOS) were quantitatively analyzed. Lipid peroxidation and levels of reactive oxygen species (ROS) were also determined. Rosemary decreased lipid peroxidation in both brain tissues. The levels of catalase activities in heart and cortex were decreased in the rosemary-treated groups. The SFE rosemary-treated rats presented lower NOS levels in heart and lower ROS levels in hippocampus than the control rats. Supplementing the diet of aged rats with SFE rosemary extract produced a decrease in antioxidant enzyme activity, lipid peroxidation and ROS levels that was significant for catalase activity in heart and brain, NOS in heart, and LPO and ROS levels in different brain tissues. These observations suggest that the rosemary supplement improved the oxidative stress status in old rats.
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PMID:Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats. 1928 62

We tested two hypotheses, first that exercise training reverses age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries and second that this improved endothelium-dependent dilation is the result of increased nitric oxide (NO) bioavailability due to increased content and phosphorylation of endothelial NO synthase (eNOS) and/or increased antioxidant enzyme content. Young (2 mo) and old (22 mo) male Fischer 344 rats were exercise trained (Ex) or remained sedentary (Sed) for 10-12 wk, yielding four groups of rats: 1) young Sed (4-5 mo), 2) young Ex (4-5 mo), 3) old Sed (24-25 mo), and 4) old Ex (24-25 mo). Soleus muscle feed arteries (SFA) were isolated and cannulated with two glass micropipettes for examination of endothelium-dependent (ACh) and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism(s) by which exercise affected dilator responses, ACh-induced dilation was assessed in the presence of N(omega)-nitro-l-arginine (l-NNA; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), and l-NNA + Indo. Results indicated that ACh-induced dilation was blunted in old Sed SFA relative to young Sed SFA. Exercise training improved ACh-induced dilation in old SFA such that vasodilator responses in old Ex SFA were similar to young Sed and young Ex SFA. Addition of l-NNA, or l-NNA + Indo, abolished the exercise effect. Immunoblot analysis revealed that extracellular superoxide dismutase (SOD) protein content was increased by training in old SFA, whereas eNOS and SOD-1 protein content were not altered. Addition of exogenous SOD, or SOD + catalase, improved ACh-induced dilation in old Sed SFA such that vasodilator responses were similar to young Sed SFA. Addition of l-NNA abolished the effect of exogenous SOD in old Sed arteries. Collectively, these results indicate that exercise training reverses age-induced endothelial dysfunction in SFA by increasing NO bioavailability and that increases in vascular antioxidant capacity may play an integral role in the improvement in endothelial function.
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PMID:Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries. 1929 69

Age is the major risk factor for cardiovascular diseases (CVD) and this is attributable in part to stiffening of large elastic arteries and development of vascular endothelial dysfunction (e.g. impaired endothelium-dependent dilatation, EDD). In contrast, regular aerobic exercise is associated with reduced risk of CVD. Endurance exercise-trained middle-aged/older adults demonstrate lower large elastic artery stiffness and greater EDD than their sedentary peers. With daily brisk walking, previously sedentary middle-aged/older adults show reduced stiffness and improved EDD. The mechanisms underlying the effects of regular aerobic exercise on large elastic artery stiffness with ageing are largely unknown, but are likely to include changes to the composition of the arterial wall. Enhanced EDD in older adults who exercise is mediated by increased nitric oxide (NO) bioavailability associated with reduced oxidative stress. Arteries from old rodents that perform regular aerobic exercise demonstrate increased expression and activity of endothelial NO synthase, reduced oxidative damage associated with reduced expression and activity of the oxidant enzyme NADPH oxidase, and increased activity of the antioxidant enzyme superoxide dismutase. Aerobic exercise also may protect arteries with ageing by increasing resistance to the effects of other CVD risk factors like LDL-cholesterol. Habitual aerobic exercise is an effective strategy to combat arterial ageing.
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PMID:Habitual exercise and vascular ageing. 1972 76

The organic nitrate pentaerythritol tetranitrate is devoid of nitrate tolerance, which has been attributed to the induction of the antioxidant enzyme heme oxygenase (HO)-1. With the present study, we tested whether chronic treatment with pentaerythritol tetranitrate can improve angiotensin II-induced vascular oxidative stress and dysfunction. In contrast to isosorbide-5 mononitrate (75 mg/kg per day for 7 days), treatment with pentaerythritol tetranitrate (15 mg/kg per day for 7 days) improved the impaired endothelial and smooth muscle function and normalized vascular and cardiac reactive oxygen species production (mitochondria, NADPH oxidase activity, and uncoupled endothelial NO synthase), as assessed by dihydroethidine staining, lucigenin-enhanced chemiluminescence, and quantification of dihydroethidine oxidation products in angiotensin II (1 mg/kg per day for 7 days)-treated rats. The antioxidant features of pentaerythritol tetranitrate were recapitulated in spontaneously hypertensive rats. In addition to an increase in HO-1 protein expression, pentaerythritol tetranitrate but not isosorbide-5 mononitrate normalized vascular reactive oxygen species formation and augmented aortic protein levels of the tetrahydrobiopterin-synthesizing enzymes GTP-cyclohydrolase I and dihydrofolate reductase in angiotensin II-treated rats, thereby preventing endothelial NO synthase uncoupling. Haploinsufficiency of HO-1 completely abolished the beneficial effects of pentaerythritol tetranitrate in angiotensin II-treated mice, whereas HO-1 induction by hemin (25 mg/kg) mimicked the effect of pentaerythritol tetranitrate. Improvement of vascular function in this particular model of arterial hypertension by pentaerythritol tetranitrate largely depends on the induction of the antioxidant enzyme HO-1 and identifies pentaerythritol tetranitrate, in contrast to isosorbide-5 mononitrate, as an organic nitrate able to improve rather than to worsen endothelial function.
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PMID:Pentaerythritol tetranitrate improves angiotensin II-induced vascular dysfunction via induction of heme oxygenase-1. 2015 49

Protein sulfenic acids have been proposed as potential biochemical switches for redox signaling. This post-translational modification (PTM) is readily reversible, in contrast to some other types of oxidative PTM. Enhanced oxidative stress has been reported as a feature of hypertension, and renal function has been implicated in the development and progression of the disease in animal models such as the spontaneously hypertensive rat (SHR). However, reactive oxygen species (ROS) are also signaling molecules and may play a role in vascular function. To investigate protein sulfenation under hypertensive conditions, we examined protein extracts of SHR kidney medulla in comparison to medulla from normotensive Wistar rats. Total free thiol content of the SHR medulla was significantly lower than that of Wistar medulla, indicating enhanced oxidation of sulfhydryls. Protein sulfenation was also significantly greater in the medulla of hypertensive animals. Thioredoxin reductase activity was also reduced in SHR medulla and this may account, in part, for enhanced protein sulfenation. Purification of sulfenated proteins from SHR medulla revealed several proteins involved in processes such as metabolism, antioxidant defense, and regulation of nitric oxide synthase. Enhanced sulfenation may represent perturbed redox signaling in SHR medulla, or simply enhanced ROS generation.
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PMID:Proteomic profiling of perturbed protein sulfenation in renal medulla of the spontaneously hypertensive rat. 2035 67


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