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)

Changes in zinc (Zn) metabolism and interleukin-1 beta (IL-1 beta) release occur as part of the physiological response to tissue injury and trauma. In the present study, the influence of Zn status on the response to continuous low-dose IL-1 beta administration was evaluated. Rats were fed 50 micrograms Zn/g (adequate zinc; AZn) or 5 micrograms Zn/g (marginal zinc; MZn) diets for 14 days. On day 15, rats were infused via osmotic minipumps, with IL-1 beta (2.3 ng/hr) or saline (control, C) and euthanized 1, 3, or 7 days later. In the AZn rats, IL-1 beta infusion resulted in increased plasma copper (Cu) concentrations and ceruloplasmin (Cp) activity, and decreased iron (Fe) concentrations throughout the 7d period. These effects were most pronounced on d1 and d3. A similar trend was observed in the MZn rats, but IL-1 beta-induced increases in plasma Cu and Cp activity were less than in the AZn fed rats. In MZn and AZn IL-1 beta infused rats, plasma Zn was decreased on Day 1, and Day 3, respectively, compared with their respective controls. AZn IL-1 beta-infused rats were characterized by high liver Fe, Zn, and metallothionein (MT) concentrations on Day 1; by Day 7, only MT concentrations remained elevated. Liver MnSOD activity was 13%-29% higher in both the AZn- and MZn-IL-1 beta-infused rats than their respective controls on Day 3 and Day 7, with most significant increase observed on Day 7. These data show that Zn status can influence the response to low-dose IL-1 beta; this influence of Zn should be considered when IL-1 beta is given therapeutically.
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PMID:Zinc status and interleukin-1 beta-induced alterations in mineral metabolism in rats. 807 54

The cytokine IL-1 beta has previously been demonstrated to induce the expression of the stress genes iNOS, hsp70, heme oxygenase and Mn-SOD in rat pancreatic islets in vitro. The aim of this study was to determine whether the IL-1 beta-induced effects are specific for the insulin producing beta-cell, or whether other islet cells, such as the glucagon-producing alpha-cell, respond to IL-1 beta addition. Purified rat alpha- and beta-cell suspensions were obtained by fluorescence-activated cell sorting and incubated with or without IL-1 beta (25 U/ml) for 24 h. The alpha- and beta-cell contents of hsp70, heme oxygenase and Mn-SOD and medium nitrite levels were determined. It was found that IL-1 beta exposure induced the production of nitric oxide in beta-cells, but not in alpha-cells. Moreover, the expression of hsp70, heme oxygenase and Mn-SOD was also induced in beta-cells, but not in alpha-cells. There were no detectable levels of hsp70 in alpha-cells. It is concluded that the stress gene response following IL-1 beta exposure is markedly different in alpha- and beta-cells. This finding may be of importance for the understanding of the autoimmune destruction of beta-cells in insulin-dependent diabetes mellitus.
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PMID:Interleukin-1 beta induces the expression of hsp70, heme oxygenase and Mn-SOD in FACS-purified rat islet beta-cells, but not in alpha-cells. 871 14

Epiandrosterone (EA), dehydroepiandrosterone (DHEA), and their sulfate (-S) and acetate (-A) conjugates were investigated for effects on isolated pancreatic islets and RINm5F insulinoma cells. Interleukin-1 beta (IL-1 beta) inhibited glucose-stimulated insulin release in cultured islets, but the presence of EA, EA-A, and to a lesser extent EA-S, preserved the secretory response. IL-1 beta also increased islet nitrite production, which was antagonized by EA and EA-A, but not by EA-S. EA, EA-A, DHEA, and DHEA-A, but not EA-S and DHEA-S inhibited glucose-stimulated insulin release from islets. This response may be related to the inhibition of glucose transport by EA, EA-A, DHEA, DHEA-A, and DHEA-S, as observed in RINm5F cells. EA, EA-A, DHEA, and DHEA-A also inhibited glucose metabolism in RINm5F cells, whereas EA-S and DHEA-S had no effect. EA, EA-A, DHEA, and DHEA-A, but not the sulfate conjugates, also inhibited RINm5F cell IL-1 beta-induced nitric oxide synthase (iNOS) activity. IL-1 beta also increased cytosolic Cu/Zn-superoxide dismutase (SOD) and mitochondrial Mn-SOD in RINm5F cells. EA inhibited RINm5F cell Cu/Zn-SOD in the presence and absence of IL-1 beta, whereas EA-S increased basal enzyme activity and did not affect the IL-1 beta response. EA did not affect basal Mn-SOD activity and inhibited IL-1 beta-stimulated activity, whereas EA-S was without effect. IL-1 beta had no effect on catalase activity in RINm5F cells, whereas EA, EA-A, and DHEA-A inhibited catalase activity. Thus, EA and DHEA and their acetate congeners protected the beta-cell from the inhibitory effects of IL-1 beta, and inhibited glucose transport and oxidation, and inducible nitricoxide synthase expression. EA and DHEA also had profound effects on Cu/Zn-SOD, which may alter the toxic effects of hydrogen peroxide generation in beta-cells.
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PMID:Rat pancreatic islet and RINm5F cell responses to epiandrosterone, dehydroepiandrosterone and interleukin-1 beta. 1007 38

Phenotypic modulation of endothelium to a dysfunctional state contributes to the pathogenesis of cardiovascular diseases such as atherosclerosis. The localization of atherosclerotic lesions to arterial geometries associated with disturbed flow patterns suggests an important role for local hemodynamic forces in atherogenesis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical forces generated by pulsatile blood flow, can discriminate among these stimuli and transduce them into genetic regulatory events. At the level of individual genes, this regulation is accomplished via the binding of certain transcription factors, such as NF kappa B and Egr-1, to shear-stress response elements (SSREs) that are present in the promoters of biomechanically inducible genes. At the level of multiple genes, distinct patterns of up- and downregulation appear to be elicited by exposure to steady laminar shear stresses versus comparable levels of non-laminar (e.g., turbulent) shear stresses or cytokine stimulation (e.g., IL-1 beta). Certain genes upregulated by steady laminar shear stress stimulation (such as eNOS, COX-2, and Mn-SOD) support vasoprotective (i.e., anti-inflammatory, anti-thrombotic, anti-oxidant) functions in the endothelium. We hypothesize that the selective and sustained expression of these and related "atheroprotective genes" in the endothelial lining of lesion-protected areas represents a mechanism whereby hemodynamic forces can influence lesion formation and progression.
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PMID:Endothelial dysfunction, hemodynamic forces, and atherogenesis. 1086 43

The effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and H2O2, on hepatitis B virus (HBV) replication was analyzed in the HBV DNA transfected human hepatoblastoma-derived cell line HB 611. Secretion of HBV DNA from HB611 cells was inhibited by IFN-gamma, TNF-alpha, IL-1beta, and H2O2 in a dose-dependent manner. These cytokines and H2O2 also decreased HBV mRNA expression in HB611 cells, meaning that these reagents decreased the synthesis of all virally encoded components of the HBV virion. The level of manganese-SOD mRNA, indicative of occurrence of oxidative stress, increased immediately after treatment with IFN-gamma, TNF-alpha, IL-1beta, and H2O2. Moreover, the antioxidant N-acetyl-L-cysteine substantially inhibited the antiviral effect. Our findings suggest that oxidative stress may be a common factor in the antiviral effects of IFN-gamma, TNF-alpha, and IL-1beta on HBV.
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PMID:Interferon-gamma, tumor necrosis factor-alpha, and interleukin 1-beta suppress the replication of hepatitis B virus through oxidative stress. 1158 67

The transcription factor activator protein (AP)-1 plays crucial roles in proliferation, cell death, and the immune response. c-JUN is an important component of AP-1, but only very few c-JUN response genes have been identified to date. Activity of c-JUN is controlled by NH2-terminal phosphorylation (JNP) of its transactivation domain by a family of JUN-NH2-terminal protein kinases (JNK). JNK form a stable complex with c-JUN in vitro and in vivo. We have targeted this interaction by means of a cell-permeable peptide containing the JNK-binding (delta) domain of human c-JUN. This peptide strongly and specifically induced apoptosis in HeLa tumor cells, which was paralleled by inhibition of serum-induced c-JUN phosphorylation and up-regulation of the cell cycle inhibitor p21cip/waf. Application of the c-JUN peptide to interleukin (IL)-1-stimulated human primary fibroblasts resulted in up-regulation of four genes, namely COX-2, MnSOD, I kappa B alpha, and MAIL and down-regulation of 10 genes, namely CCL8, mPGES, SAA1, hIAP-1, hIAP-2, pent(r)axin-3, CXCL10, IL-1 beta, ICAM-1, and CCL2. Only a small group of genes, namely pent(r)axin-3, CXCL10, ICAM-1, and IL-1 beta, was inhibited by both the c-JUN peptide and the JNK inhibitor SP600125. Thereby, and by additional experiments using small interfering RNA to suppress endogenous c-JUN we identify for the first time three distinct groups of inflammatory genes whose IL-1-induced expression depends on c-JUN, on JNK, or on both. These results shed further light on the complexity of c-JUN-JNK-mediated gene regulation and also highlight the potential use of dissecting signaling downstream from JNK to specifically target proliferative diseases or the inflammatory response.
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PMID:Disruption of the c-JUN-JNK complex by a cell-permeable peptide containing the c-JUN delta domain induces apoptosis and affects a distinct set of interleukin-1-induced inflammatory genes. 1283 16