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)

Renal ischemia-reperfusion (I-R) contributes to the development of ischemic acute renal failure (ARF). Multi-factorial processes are involved in the development and progression of renal I-R injury with the generation of reactive oxygen species, nitric oxide and peroxynitrite, and the decline of antioxidant protection playing major roles, leading to dysfunction, injury, and death of the cells of the kidney. Renal inflammation, involving cytokine/adhesion molecule cascades with recruitment, activation, and diapedesis of circulating leukocytes is also implicated. Clinically, renal I-R occurs in a variety of medical and surgical settings and is responsible for the development of acute tubular necrosis (a characteristic feature of ischemic ARF), e.g., in renal transplantation where I-R of the kidney directly influences graft and patient survival. The cellular mechanisms involved in the development of renal I-R injury have been targeted by several pharmacological interventions. However, although showing promise in experimental models of renal I-R injury and ischemic ARF, they have not proved successful in the clinical setting (e.g., atrial natriuretic peptide, low-dose dopamine). This review highlights recent pharmacological developments, which have shown particular promise against experimental renal I-R injury and ischemic ARF, including novel antioxidants and antioxidant enzyme mimetics, nitric oxide and nitric oxide synthase inhibitors, erythropoietin, peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP-ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine. Novel approaches such as recent research involving combination therapies and the potential of non-pharmacological strategies are also considered.
 ...
PMID:Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review. 1803 25

Tumor necrosis factor-alpha (TNF-alpha), a ubiquitous pro-inflammatory cytokine, is an important mediator in the immune-neuroendocrine system that affects the CNS. The present study demonstrates that treatment with TNF-alpha activates microglia to increase TNF-alpha production in primary cultures of glial cells isolated from wild-type (WT) mice and mice deficient in the inducible form of nitric oxide synthase (iNOSKO). However, mitochondrial dysfunction in WT neurons occurs at lower concentrations of TNF-alpha when neurons are directly treated with TNF-alpha or co-cultured with TNF-alpha-treated microglia than iNOSKO neurons similarly treated. Immunofluorescent staining of primary neurons co-cultured with TNF-alpha-treated microglia reveals that the antioxidant enzyme in mitochondria, manganese superoxide dismutase (MnSOD), is co-localized with nitrotyrosine in WT but not in iNOSKO primary neuronal cells. Importantly, the percentage of surviving neurons is significantly reduced in WT neurons compared with iNOSKO neurons under identical treatment conditions. Together, the results suggest that TNF-alpha activates microglia to produce high levels of TNF-alpha and that production of nitric oxide (NO) in neurons is an important factor affecting MnSOD nitration and subsequent mitochondrial dysfunction.
 ...
PMID:Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells. 1816 Feb 24

Extracellular superoxide dismutase (ecSOD) is the major extracellular scavenger of superoxide (O(2)(.-)) and a main regulator of nitric oxide (NO) bioactivity in the blood vessel wall, heart, lungs, kidney, and placenta. Involvement of O(2)(.-) has been implicated in many pathological processes, and removal of extracellular O(2)(.-) by ecSOD gene transfer has emerged as a promising experimental technique to treat vascular disorders associated with increased oxidant stress. In addition, recent studies have clarified mechanisms that regulate ecSOD expression, tissue binding, and activity, and they have provided new insight into how ecSOD interacts with other factors that regulate vascular function. Finally, studies of a common gene variant in humans associated with disruption of ecSOD tissue binding suggest that displacement of the enzyme from the blood vessel wall may contribute to vascular diseases. The purpose of this review is to summarize recent research findings related to ecSOD function and gene transfer and to stimulate other investigations into the role of this unique antioxidant enzyme in vascular pathophysiology and therapeutics.
 ...
PMID:Extracellular superoxide dismutase (ecSOD) in vascular biology: an update on exogenous gene transfer and endogenous regulators of ecSOD. 1820 74

The present study was designed to evaluate the effects of three nonsteroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal antioxidant enzyme status and surface characteristics during 1,2-dimethylhydrazine (DMH) administration. Male Sprague-Dawley rats were divided into five different groups: Group 1 (control, vehicle treated); group 2 (DMH treated, 30 mg/kg body weight/week, subcutaneously); group 3 (DMH + aspirin 60 mg/kg body weight); group 4 (DMH + celecoxib 6 mg/kg body weight); group 5 (DMH + etoricoxib 0.64 mg/kg body weight). Postmitochondrial fraction were isolated from the intestinal segments and different oxidative parameters and other parameters studied, such as the lipid peroxides, reduced and total glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, nitric oxide, citrulline, and nucleic acids. At the end of 6 weeks of treatment, the results indicated a significant alteration in the antioxidative defense status of the intestine in the presence of the procarcinogen DMH, which was restored with the administration of NSAIDs. The study, therefore, suggests a possible mechanism for the chemopreventive effects of NSAIDs against the experimental intestinal cancer in rats.
 ...
PMID:Effect of nonsteroidal anti-inflammatory drugs and the procarcinogen 1,2-dimethylhydrazine on the antioxidant defense system. 1840 40

Metastatic cancer is a complex positive feedback loop system. Such as system has a tendency to acquire extreme robustness. Signaling pathways controlling that robustness can fail completely if an essential element from the signaling is removed. That element is a locus of fragility. Targeting that locus represents the best way to target the cancer robustness. This prospect presents another locus of fragility in signaling complex system network, controlling the cell cycle progression through the PI3K/AKT/mTOR/RAN pathway and cell migration and angiogenesis through the VEGF/PI3K/AKT/NO/ICAM-1 pathway. The locus of fragility of these pathways is AKT, which is regulated by a balance of catalase/H2O2 or by AKT inhibitor. Tiny and trivial perturbations such as change in redox state in the cells by antioxidant enzyme catalase, scavenging H2O2 signaling molecule, regulates robust signaling molecule AKT, abolishing its phosporilation and inducing cascading failure of robust signaling pathways for cell growth, proliferation, migration, and angiogenesis. An anticancer effect of the antioxidant is achieved through the AKT locus, by abolishing signals from growth factors VEGF, HGF, HIF-1alpha and H2O2. Previously reported locus of fragility nitric oxide (NO) and locus AKT are close in the complex signaling interactome network, but they regulate distinct signaling modules. Simultaneously targeted loci represents new principles in cancer robustness chemotherapy by blocking cell proliferation, migration, angiogenesis and inducing rather slow then fast apoptosis leading to slow eradication of cancer.
 ...
PMID:AKT as locus of fragility in robust cancer system. 1842 70

This study aims at observing the effect of low-density lipoprotein (LDL) receptor deficiency in cholesterol blood levels, baroreflex sensitivity (BRS), nitric oxide (NO) bioavailability, and oxidative stress. The lack of LDL receptors in mice significantly increased the cholesterol blood levels (179+/-35 vs. 109+/-13mg/dL) in the knockout (KO) mice compared to control. There was no difference in basal mean arterial pressure and heart rate between the groups. However, in KO mice the BRS was significantly attenuated and the antioxidant enzyme activities, measured in erythrocytes and heart, were significantly decreased. On the other hand, the oxidative damage measured by chemiluminescence and carbonyls was increased, while total plasma nitrate levels were lower in KO mice, indicating a decrease in NO availability. In conclusion, these results indicate that the lack of LDL receptor increased cholesterol blood levels, induced oxidative stress and decreased BRS.
 ...
PMID:Baroreflex sensitivity and oxidative stress in the LDL receptor knockout mice. 1843 14

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.
 ...
PMID:Ameliorative effects of lotus seedpod proanthocyanidins on cognitive deficits and oxidative damage in senescence-accelerated mice. 1865 48

The sea anemone Aiptasia pallida, symbiotic with intracellular dinoflagellates, expresses a peptydyl-prolyl cis-trans isomerase (PPIase) belonging to the conserved family of cytosolic cyclophilins (ApCypA). Protein extracts from A. pallida exhibited PPIase activity. Given the high degree of conservation of ApCypA and its known function in the cellular stress response, we hypothesized that it plays a similar role in the cnidarian-dinoflagellate symbiosis. To explore its role, we inhibited the activity of cyclophilin with cyclosporin A (CsA). CsA effectively inhibited the PPIase activity of protein extracts from symbiotic A. pallida. CsA also induced the dose-dependent release of symbiotic algae from host tissues (bleaching). Laser scanning confocal microscopy using superoxide and nitric oxide-sensitive fluorescent dyes on live specimens of A. pallida revealed that CsA strongly induced the production of these known mediators of bleaching. We tested whether the CsA-sensitive isomerase activity is important for maintaining the activity of the antioxidant enzyme superoxide dismutase (SOD). SOD activity of protein extracts was not affected by pre-incubation with CsA in vitro.
 ...
PMID:Cyclophilin and the regulation of symbiosis in Aiptasia pallida. 1872 38

Cyclosporine A is a well-known immunosuppressor agent universally used in allotransplantation. However, it has been demonstrated that this drug produces side-effects in several organs, particularly in the kidney and in the heart. Nigella sativa oil has long been used in folk medicine for a wide range of illnesses. One of the potential properties of N. sativa oil is the ability of one or more of its constituents to reduce toxicity due to its antioxidant activities. The antioxidant effects of N. sativa oil have been examined using different hepatic and kidney toxicity in in vivo murine models. The aim of this study was to evaluate the effects of N. sativa oil in the antioxidant enzyme status and myocardium of cyclosporine-A-treated rats. This study included 24 male Wistar albino young healthy rats (8-12 weeks) weighing 150-200 g. The control group received sunflower oil (21 days, 2 ml/kg/day, orally) without any treatment. The second group received only N. sativa oil (21 days, 2 ml/kg, orally) (N. sativa oil group). The animals in the third group received only cyclosporine A (21 days, 25 mg/kg, orally) (cyclosporine A group). The animals in the fourth group were treated with cyclosporine A (21 days, 25 mg/kg, orally) and starting one day before cyclosporine A administration were treated with N. sativa oil (21 days, 2 ml/kg, orally) (cyclosporine A +N. sativa oil group). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the heart tissues were significantly reduced in the cyclosporine A group compared to control values. Nigella sativa oil treatment caused an increase in the activities of SOD, CAT and GSH-Px compared to the control group. Malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were increased in the cyclosporine A-treated group in comparison with the control and N. sativa groups. Co-administration of N. sativa oil and cyclosporine A abrogated the cyclosporine A-induced MDA, N. sativa oil and PC increase compared to the cyclosporine A group. The results of our study show that pre-treatment with N. sativa oil reduced the subsequent cyclosporine A injury in rat heart, demonstrated by normalized cardiac histopathology, decrease in lipid peroxidation, improvement in antioxidant enzyme status and cellular protein oxidation.
 ...
PMID:Cardioprotective effects of Nigella sativa oil on cyclosporine A-induced cardiotoxicity in rats. 1880 Oct 29

Salt stress induced an increase in endogenous carbon monoxide (CO) production and the activity of the CO synthetic enzyme haem oxygenase (HO) in wheat seedling roots. In addition, a 50% CO aqueous solution, applied daily, not only resulted in the enhancement of CO release, but led to a significant reversal in dry weight (DW) and water loss caused by 150 mm NaCl treatment, which was mimicked by the application of two nitric oxide (NO) donors sodium nitroprusside (SNP) and diethylenetriamine NO adduct (DETA/NO). Further analyses showed that CO, as well as SNP, apparently up-regulated H(+)-pump and antioxidant enzyme activities or related transcripts, thus resulting in the increase of K/Na ratio and the alleviation of oxidative damage. Whereas, the CO/NO scavenger haemoglobin (Hb), NO scavenger or synthetic inhibitor methylene blue (MB) or N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME) differentially blocked these effects. Furthermore, CO was able to mimic the effect of SNP by strongly increasing NO release in the root tips, whereas the CO-induced NO signal was quenched by the addition of l-NAME or cPTIO, the specific scavenger of NO. The results suggested that CO might confer an increased tolerance to salinity stress by maintaining ion homeostasis and enhancing antioxidant system parameters in wheat seedling roots, both of which were partially mediated by NO signal.
 ...
PMID:Carbon monoxide enhances salt tolerance by nitric oxide-mediated maintenance of ion homeostasis and up-regulation of antioxidant defence in wheat seedling roots. 1881 35


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