Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of cytokines on extracellular superoxide dismutase (EC-SOD) expression by human dermal fibroblasts was investigated. The expression was markedly stimulated by interferon-gamma (IFN-gamma), was varying between fibroblast lines stimulated or depressed by interleukin-1 alpha (IL-1 alpha), was intermediately depressed by tumor necrosis factor-alpha (TNF-alpha), and markedly depressed by transforming growth factor-beta (TGF-beta). TNF-alpha, however, enhanced the stimulation by a high dose of IFN-gamma, whereas TGF-beta markedly depressed the stimulations given by IFN-gamma and IL-1 alpha. The ratio between the maximal stimulation and depression observed was around 30-fold. The responses were generally slow and developed over periods of several days. There were no effects of IFN-alpha, IL-2, IL-3, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, human growth hormone, Escherichia coli lipopolysaccharide, leukotriene B4, prostaglandin E2, formylmethionylleucylphenylalanine, platelet-activating factor, and indomethacin. The cytokines influencing the EC-SOD expression are also known to influence superoxide production by leukocytes and other cell types, and the EC-SOD response pattern is roughly compatible with the notion that its function is to protect cells against extracellular superoxide radicals. The results show that EC-SOD is a participant in the complex inflammatory response orchestrated by cytokines. The CuZn-SOD activity of the fibroblasts was not influenced by any of the cytokines, whereas the Mn-SOD activity was depressed by TGF-beta. TNF-alpha, IL-1 alpha, and IFN-gamma stimulated the Mn-SOD activity, as previously known, and these responses were reduced by TGF-beta. The different responses of the three SOD isoenzymes illustrate their different physiological roles.
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PMID:Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isoenzymes in fibroblasts. 155 78

We examined the effect of lipopolysaccharide (LPS) treatment on the expression of manganese and copper/zinc superoxide dismutase (MnSOD and Cu/ZnSOD) mRNA and protein in resident peritoneal macrophages and lung endothelial cells derived from LPS-sensitive (LPS-s) and LPS-resistant (LPS-r) mice. Macrophages from both LPS-s and LPS-r mice treated with LPS for 24 h produced increased levels of MnSOD mRNA and protein. In contrast, levels of lung endothelial cell MnSOD mRNA and protein from LPS-s mice were increased by LPS treatment, while no increases in these parameters were observed in endothelial cells from LPS-r mice. Tumor necrosis factor-alpha (TNF alpha) treatment, however, did increase levels of MnSOD mRNA in both LPS-s and LPS-r endothelial cells to an equal extent. Both macrophage and endothelial cell Cu/ZnSOD mRNA and protein levels were not significantly affected by LPS treatment. These results demonstrate that the mutation that affects susceptibility to LPS in LPS-r mice exerts a differential influence on MnSOD inducibility in a cell specific manner.
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PMID:Mn and Cu/Zn SOD expression in cells from LPS-sensitive and LPS-resistant mice. 155 15

The effects of phorbol ester (TPA) and other known stimulators such as tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide on induction of mRNA for manganese-superoxide dismutase (Mn-SOD) were investigated in various cell lines. TPA enhanced Mn-SOD mRNA expression in TNF-resistant cell lines including HeLa cells, in which the other reagents also induced expression of the gene, but did not affect TNF-sensitive cells, in which the other stimulators did not alter expression of the gene. HeLa cells which had been desensitized to TPA by pretreatment with TPA for 24 h expressed Mn-SOD mRNA at a slightly higher level than the cells without TPA treatment. TPA-pretreated cells stimulated with TNF, however, expressed Mn-SOD mRNA at about twice the level of TNF-stimulated, TPA-untreated cells. When protein synthesis was inhibited by cycloheximide during TPA pretreatment, TNF no more enhanced the Mn-SOD mRNA accumulation. These data suggest that at least two separate signal-transducing pathways are involved in expression of this gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulation with TNF, interleukin-1, or lipopolysaccharide and in which a protein factor that can be induced by TPA treatment is involved.
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PMID:Phorbol ester induces manganese-superoxide dismutase in tumor necrosis factor-resistant cells. 174 13

Bacterial lipopolysaccharide (LPS) was shown to produce an induction of manganese superoxide dismutase (Mn SOD) mRNA levels in porcine pulmonary artery endothelial cells (PAEC). Additional studies in porcine PAEC also demonstrated induction of Mn SOD mRNA in response to the inflammatory mediators interleukin 1 and tumor necrosis factor. On the other hand, we observed no change in Mn SOD mRNA within 24 h of a hyperoxic exposure. The induction of Mn SOD by LPS was blocked by both a RNA synthesis inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide. The data implicate the involvement of Mn SOD in the acute phase response of pulmonary endothelial cells.
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PMID:Regulation of manganese superoxide dismutase in porcine pulmonary artery endothelial cells. 205 89

We have demonstrated a dramatic induction of manganese superoxide dismutase (Mn-SOD) mRNA levels in response to lipopolysaccharide (LPS), interleukin-1, and tumor necrosis factor in pulmonary epithelial cells. These stimuli had no effect on the corresponding mRNA levels for the copper/zinc (Cu/Zn)-SOD. Identical treatments of pulmonary fibroblast cells with LPS showed only minor changes in the Mn-SOD mRNA levels demonstrating a cell type-specific effect for this acute inflammatory mediator. Furthermore, we have shown that hyperoxia has no effect within 24 h on Mn-or Cu/Zn-SOD mRNA levels in either fibroblasts or epithelial cells. The induction of Mn-SOD mRNA levels by LPS is completely inhibited by actinomycin. Treatment of cells with cycloheximide causes an induction equal to that for LPS, whereas co-treatment with cycloheximide and LPS resulted in a "super induction." This data is strongly suggestive of an important role for the Mn-SOD in the acute inflammatory response.
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PMID:Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response. 240 41

Superoxide dismutases (SODs) scavenge superoxide anion and participate in an essential role as a defense system against oxidative stress in body. Cu,Zn-SOD is localized at cytoplasm. A defect in the Cu,Zn-SOD gene has been demonstrated in some cases of familial amyotrophic lateral sclerosis. Trisomy of chromosome 21 in Down's syndrome increases the level of this isozyme and causes the disease. Inactivation of Cu,Zn-SOD by glycation under hyperglycemic conditions may also be a critical factor for diabetic complication. The expression of the second isozyme, Mn-SOD localized at mitochondrial matrix, is regulated in a complex manner by many stimulants such as interleukin-1, -6, tumor necrosis factor, lipopolysaccharide, and tumor promoters phorbol ester (TPA) and okadaic acid. This isozyme seems to work as a defense mechanism against damage during inflammatory responses. The third isozyme, extracellular SOD, is highly glycosylated and has affinity for heparin sulfate. This may participate in scavenging superoxide in plasma and, therefore, missense mutation in heparin binding domain increases the serum level of this isozyme, although the physiological role is not clearly understood yet.
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PMID:[Physiological significance of superoxide dismutase isozymes]. 760 83

Two experiments were conducted to examine the effect of dietary Cu level on Cu metabolism during the acute phase response in broiler chicks with adequate (Experiment 1) or deficient (Experiment 2) Cu. Diets based on cornstarch and isolated soybean protein were used to formulate a basal diet, and basal diet plus either 5, 10, or 15 mg/kg additional Cu as either CuO or CuSO4. Each diet was fed to six pens of five chicks per pen (Experiment 1) or eight pens of five chicks (Experiment 2). Half of the chicks on each diet were injected with Salmonella typhymurium lipopolysaccharide (LPS) on alternate days. In Experiment 1, LPS significantly decreased daily gain, feed intake, and feed efficiency (P < 0.01) and increased the concentration of Cu in blood plasma (P < 0.01). In the uninjected birds, adding 5, 10, or 15 mg/kg Cu as CuO or 15 mg/kg Cu as CuSO4 increased the rate of gain over that of chicks fed the basal diet. In the birds challenged with LPS, 10 mg/kg Cu as CuO increased the rate of gain and efficiency compared to those of chicks fed the basal diet. Addition of CuSO4 to the diet of chicks challenged with LPS did not affect gain, intake, or feed efficiency compared to those of chicks fed the basal diet. Ceruloplasmin levels were higher in chicks challenged with LPS than in control chicks (P = 0.03), and this difference tended to be greater in chickens fed CuO than in chickens fed CuSO4 (P = 0.07). In chicks challenged with LPS, feeding CuO at all levels and feeding CuSO4 to give 10 or 15 mg/kg Cu increased ceruloplasmin levels above that of chicks fed the basal diet. Hepatic Mn superoxide dismutase (SOD) and Cu/Zn SOD were not influenced by dietary Cu level or source or LPS. Results of Experiment 2 were similar to those of Experiment 1 except that supplemental CuSO4 and CuO gave similar increases in gain and CuSO4 was more effective at increasing ceruloplasmin levels. Chicks given supplemental Cu had higher ceruloplasmin levels following challenge with LPS than Cu-deficient chicks fed the basal diet. Apparently, Cu requirements are higher for chicks experiencing an acute phase response than for healthy chicks.
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PMID:Dietary copper level affects copper metabolism during lipopolysaccharide-induced immunological stress in chicks. 880 5

Subversion of mitochondrial electron transport to the production of O2.- has been proposed as a mechanism of tumor necrosis factor (TNF)-mediated cell killing and to a lesser extent interleukin-1 (IL-1) and lipopolysaccharide (LPS) cytotoxicity. We utilized the O2.- -sensitive aconitases to measure changes in steady-state 02.- levels in the mitochondrial matrix and cytoplasm of cultured mammalian cells in response to these inflammatory mediators. TNF alpha did not measurably affect aconitase activity, and thus mitochondrial 02.- production, in either cultured human A549 cells or murine L929 cells while TNF alpha clearly caused cytotoxicity as revealed by impaired mitochondrial respiration. IL-1 alpha and Escherichia coli LPS also failed to affect the aconitase activity in A549 cells. Neither the O2.- scavenger Mn(III) TMPyP nor the H2O2 scavenger catalase protected L929 cells against the cytotoxicity of TNF alpha. In conclusion, TNF, IL-1, and LPS do not appear to exert cytotoxicity, or MnSOD gene induction effects, by eliciting mitochondrial O2.- production.
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PMID:Failure of tumor necrosis factor and interleukin-1 to elicit superoxide production in the mitochondrial matrices of mammalian cells. 883 51

Reactive oxygen species (ROS) are mediators of cellular injury and play a putative role in the onset of hepatic damage during endotoxemia or sepsis. It has been suggested that induction of glucose-6-phosphate (G-6-P) dehydrogenase, the key enzyme of the hexose monophosphate shunt (HMS), may support ROS-producing or ROS-eliminating pathways in hepatic endothelial and Kupffer cells during endotoxemia. The aim of the study was to assess in vivo lipopolysaccharide (LPS)-induced alterations in rat gene expression of selected enzymes that are in functional relationship with the HMS. mRNA levels and activities of glucose transporter GLUT-1, Mn- and CuZn-dependent superoxide dismutases (Mn-SOD and CuZn-SOD), and Se-dependent glutathione peroxidase (Se-GPX) were determined. Cellular extracts were analyzed 7 or 22 h after injection of LPS (Escherichia coli, 2 mg/kg ip) or injection of saline. Exposure to LPS for 7 or 22 h caused a 10- to 25-fold increase in GLUT-1 mRNA levels in endothelial and Kupffer cells. In parenchymal cells, GLUT-1 mRNA expression was low, and LPS caused no marked changes. Cellular levels of Mn-SOD mRNA were 20-40 times greater in all hepatic cells from LPS-treated animals than in cells from control rats. LPS at 22 h increased Mn-SOD activity by 45% in endothelial cells but caused no significant changes in Kupffer or parenchymal cells. Message levels and enzyme activities of CuZn-SOD and Se-GPX were significantly elevated 22 h after LPS injection in endothelial cells only. Thus LPS results in marked upregulation of functionally related genes in hepatic cells. In endothelial cells, the simultaneous upregulation of GLUT-1, G-6-P dehydrogenase, Mn-SOD, CuZn-SOD, and Se-GPX may represent an important mechanism for accelerated elimination of ROS released from activated sinusoidal phagocytes. In Kupffer cells, upregulated GLUT-1 and G-6-P dehydrogenase, together with constitutively present SOD and lack of upregulated Se-GPX, suggest an elevated capacity to produce O2- and H2O2 that is consistent with primed bacterial killing.
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PMID:Endotoxin stimulates gene expression of ROS-eliminating pathways in rat hepatic endothelial and Kupffer cells. 892 96

Cytosolic and mitochondrial alterations induced by exposure of rat astroglial primary cultures to reactive oxygen species (ROS) generated by a xanthine/xanthine oxidase (X/XO) mixture or by lipopolysaccharide (LPS) have been investigated biochemically and immunochemically. In the presence of ROS generated by X/XO, a significant decrease in Cu,Zn superoxide dismutase (Cu,Zn-SOD) and in glutamine synthetase (GS) activity was observed whereas mitochondrial Mn-SOD activity and enzyme protein levels were significantly enhanced. Similar effects on GS, Cu,Zn- and Mn-SOD activities were observed by glucose/glucose oxidase treatment of the cells. Addition of LPS to the cell growth medium also specifically induces Mn-SOD synthesis but was without effect on Cu,Zn-SOD. It is suggested that in all these tested situations, hydrogen peroxide could represent a specific inducer of the observed phenomenon and it may therefore be considered as an intracellular messenger involved in the regulation of some aspects of astroglial oxidative metabolism, particularly the defence against ROS.
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PMID:Modulation of oxygen-radical-scavenging enzymes by oxidative stress in primary cultures of rat astroglial cells. 894 Jun 11


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