Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to test the hypothesis that increased flow through coronary arterioles increases endothelial cell nitric oxide synthase (ecNOS) and Cu/Zn superoxide dismutase (SOD) mRNA expression. Single porcine coronary arterioles (ID 100-160 micrometers; pressurized) were cannulated, perfused, and exposed to intraluminal flow sufficient to produce maximal flow-induced dilation of coronary arterioles (high flow; 7.52 +/- 0.22 microliter/min), low flow (0.84 +/- 0.05 microliter/min), or no flow for 2 or 4 h. Mean shear stress was calculated to be 5.7 +/- 1.0 dyn/cm2 for high-flow arterioles and 1. 6 +/- 1.0 dyn/cm2 for low-flow arterioles. At the end of the treatment period, mRNA was isolated from each vessel, and ecNOS and SOD mRNA expression was assessed using a semiquantitative RT-PCR. All data were standardized by coamplifying ecNOS or SOD with glyceraldehyde-3-phosphate dehydrogenase. The results indicate that ecNOS mRNA expression is increased in arterioles exposed to 2 or 4 h of high flow. In contrast, SOD mRNA expression was increased only after 4 h of high flow. Neither gene is induced by exposure to low flow. On the basis of these data, we concluded that ecNOS and SOD mRNA expression is regulated by flow in porcine coronary arterioles. In addition, we concluded that a threshold level of flow and shear stress must be sustained to elicit the upregulation of ecNOS and SOD mRNA expression.
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PMID:Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary arterioles. 1007 92

The expression of the HIV-1 Tat protein in HeLa cells resulted in a 2.5-fold decrease in the activity of the antioxidant enzyme glutathione peroxidase (GPX). This decrease seemed not to be due to a disturbance in selenium (Se) uptake. Indeed, the intracellular level of Se was similar in parental and tat-transfected cells. A Se enrichment of the medium did not lead to an identical GPX activity in both cell lines, suggesting a disturbance in Se utilization. Total intracellular 75Se selenoproteins were analyzed. Several quantitative differences were observed between parental and tat-transfected cells. Mainly, cytoplasmic glutathione peroxidase and a 15-kDa selenoprotein were decreased in HeLa-tat cells, while phospholipid hydroperoxide glutathione peroxidase and low-molecular-mass selenocompounds were increased. Thioredoxin reductase activity and total levels of 75Se-labeled proteins were not different between the two cell types. The effect of Tat on GPX mRNA levels was also analyzed. Northern blots revealed a threefold decrease in the GPX/glyceraldehyde phosphate dehydrogenase mRNA ratio in HeLa-tat versus wild type cells. By deregulating the intracellular oxidant/antioxidant balance, the Tat protein amplified UV sensitivity. The LD50 for ultraviolet radiation A was 90 J/cm2 for HeLa cells and only 65 J/cm2 for HeLa-tat cells. The oxidative stress occurring in the Tat-expressing cells and demonstrated by the diminished ratio of reduced glutathione/oxidized glutathione was not correlated with the intracellular metal content. Cellular iron and copper levels were significantly decreased in HeLa-tat cells. All these disturbances, as well as the previously described decrease in Mn superoxide dismutase activity, are part of the viral strategy to modify the redox potential of cells and may have important consequences for patients.
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PMID:Human immunodeficiency virus type 1 Tat protein impairs selenoglutathione peroxidase expression and activity by a mechanism independent of cellular selenium uptake: consequences on cellular resistance to UV-A radiation. 1136 44

The pine vole, Microtus pinetorum, was evaluated as a laboratory animal model for infection with Rickettsia rickettsii. Voles demonstrated signs of acute disease, and 45% of infected animals died following intraperitoneal infection with 3 x 10(6) plaque forming units of R. rickettsii. Spleen, liver, kidney, lung, brain, testes and blood were analyzed for rickettsial burden by a quantitative PCR assay. The distribution of rickettsiae in tissues during the course of infection was determined by immunohistochemical staining and pathological changes in tissues were correlated with the clinical severity of infection. Quantitative RT-PCR assays were designed to measure the mRNA levels of the antioxidant enzyme genes for catalase, glutathione peroxidase, glutathione reductase, heme oxygenase, Cu-Zn superoxide dismutase (SOD) and Mn-SOD, and 2 housekeeping genes, actin and glyceraldehyde phosphate dehydrogenase. Tissues from acutely ill animals on days 2 to 6 of infection, convalescent animals, and uninfected control animals were studied. The number of transcripts of each enzyme gene was determined and compared to the degree of rickettsial infection present. These studies demonstrate that the pine vole is a valuable experimental model for studying infection with R. rickettsii. Our results provide the first experimental evidence that R. rickettsii causes alteration(s) of the anti-oxidant system in vivo.
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PMID:Rickettsia rickettsii infection in the pine vole, Microtus pinetorum: kinetics of infection and quantitation of antioxidant enzyme gene expression by RT-PCR. 1286 Jun 75

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
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PMID:Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy. 1534 73

We have shown previously with in vivo and in vitro animal models that the lens epithelium, in contrast to the nucleus, is remarkably resistant to hyperoxia. The main purpose of this study was to investigate the mRNA response of cultured human lens epithelial cells (LECs) to challenge by a high level of hyperbaric oxygen. Cells were treated for 3 hr with 50 atm of 99% O2, and then cultured normally for various times up to 11 days. Although the cells appeared normal immediately after the O2-treatment, they failed to grow and suffered 50% cell loss, as well as significant mitochondrial damage, during normal post-culture. Growth of the cells resumed after 3 days and by day 11, the number of O2-treated cells was the same as the controls. Remarkably, the 3 hr O2-treatment produced no immediate effects on either the cellular level of GSH, or on the activities of a number of antioxidant enzymes including glyceraldehyde-3-phosphate dehydrogenase, which is generally regarded as being highly sensitive to oxidation. In contrast, the activity of thioredoxin reductase (TrxR) was severely affected by the O2, decreasing by 51% after the 3 hr exposure. O2-induced death of the cells appeared to be caused by loss of ATP since a 31% decrease in ATP level occurred immediately after the O2-treatment, in spite of a 46% increase in lactate production. Analysis with real-time PCR showed a maximum 3-6-fold increase in mRNA levels 9 hr after the 3 hr O2-exposure for the enzymes heme oxygenase-1 (HO-1), MnSOD and TrxR1 (the cytoplasmic form of TrxR). These results were confirmed with the use of one-step RT-PCR and Northern blotting. Initial upregulation of message for HO-1 occurred a few hours before any upregulation of MnSOD could be detected, suggesting that release of free iron from the degradation of heme by HO-1 may have played a role in the upregulation of the dismutase. No significant changes in mRNA levels were observed for the antioxidant enzymes catalase, CuZnSOD, glutathione reductase and glutathione peroxidase, or for the antioxidant protein thioredoxin. Recovery of TrxR activity over a 4-day period appeared to parallel the return of the cells to a normal rate of growth. The results indicate that damaging effects of hyperoxia on cultured LECs occur primarily in the mitochondria, rather than in the cytoplasm. Cells avoid O2-induced cell death, and return to a normal rate of proliferation by upregulating mRNA levels for HO-1, MnSOD and TrxR1. It appears that full activity of TrxR1, an enzyme required for the production of deoxyribonucletides for DNA synthesis, is essential for the normal growth of O2-challenged LECs.
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PMID:Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. 1564 22