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)

Human liver manganese superoxide dismutase (Mn-SOD) was highly purified by a simple procedure and crystallized. A monoclonal antibody against Mn-SOD, whose antigen-binding epitope is a C-terminus peptide was developed. Using this antibody, an enzyme-linked immunosorbent assay (ELISA) was developed. We found that Mn-SOD is highly expressed in human ovarian cancer and the serum level of the enzyme is a useful marker for the diagnosis and monitoring of the epithelial type of ovarian cancer. Tumor necrosis factor-alpha (TNF), lipopolysaccharide, IL-1 and phorbol ester induced the m-RNA of Mn-SOD as well as protein levels in TNF-resistant cells. No such induction was observed in Cu, Zn-SOD. Studies on the induction mechanisms indicated that at least two separate signal-transducing pathways are involved in expression of the Mn-SOD gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulations with various cytokines in which a protein factor that can be induced by phorbol ester treatments is involved.
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PMID:Expression of Mn-superoxide dismutase in carcinogenesis. 130 94

Cellular protection from immune-generated oxygen free radicals is initiated by the reduction of oxygen radicals by manganese superoxide dismutase (MnSOD) and copper/zinc superoxide dismutase (Cu/ZnSOD). Using rat adult (IEC-6) and fetal (IRD-98) intestinal epithelial cell lines, factors involved in the regulation of the SODs at the messenger RNA (mRNA) level were examined. Exposure of IEC-6 and IRD-98 to Escherichia coli lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-alpha) results in a marked increase in MnSOD mRNA as early as at 1 hour. Cotreatment of cells exposed to LPS or TNF-alpha with actinomycin D or cycloheximide showed that de novo transcription but not protein synthesis is required for the LPS- and TNF-alpha-dependent induction in MnSOD mRNA. Treatment with interleukin 1 beta results in a 12-fold increase in MnSOD mRNA, but no change was observed with interleukin 6 or interferon alpha. No change was observed in the level of Cu/ZnSOD mRNA under any condition tested. The results indicate that MnSOD functions as a cytokine-regulated acute phase protein involved in cellular protection from free radical-mediated damage.
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PMID:Acute-phase induction of manganese superoxide dismutase in intestinal epithelial cell lines. 149 41

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

S-nitro-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, inactivated bovine glutathione peroxidase (GPx) in a dose- and time-dependent manner. The IC50 of SNAP for GPx was 2 microM at 1 h of incubation and was 20% of the IC50 for another thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase, in which a specific cysteine residue is known to be nitrosylated. Incubation of the inactivated GPx with 5 mM dithiothreitol within 1 h restored about 50% of activity of the start of the SNAP incubation. A longer exposure to NO donors, however, irreversibly inactivated the enzyme. The similarity of the inactivation with SNAP and reactivation with dithiothreitol of GPx to that of glyceraldehyde-3-phosphate dehydrogenase, suggested that NO released from SNAP modified a cysteine-like essential residue on GPx. When U937 cells were incubated with 100 microM SNAP for 1 h, a significant decrease in GPx activity was observed although the change was less dramatic than that with the purified enzyme, and intracellular peroxide levels increased as judged by flow cytometric analysis using a peroxide-sensitive dye. Other major antioxidative enzymes, copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase, were not affected by SNAP, which suggested that the increased accumulation of peroxides in SNAP-treated cells was due to inhibition of GPx activity by NO. Moreover, stimulation with lipopolysaccharide significantly decreased intracellular GPx activity in RAW 264.7 cells, and this effect was blocked by NO synthase inhibitor N omega-methyl-L-arginine. This indicated that GPx was also inactivated by endogenous NO. This mechanism may at least in part explain the cytotoxic effects of NO on cells and NO-induced apoptotic cell death.
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PMID:Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity. 767 30

Parenteral injection of the cytokines interleukin-1 and tumor necrosis factor, or of endotoxin (lipopolysaccharide), protects rats against lethal pulmonary oxygen toxicity. To determine the potential importance of manganese superoxide dismutase (MnSOD) in this model, we measured MnSOD mRNA and activity in lung. In addition, we confirmed that increases in activities were related to changes in MnSOD protein, which was measured using an enzyme-linked immunosorbentassay (ELISA) technique. After cytokine or endotoxin administration, increases in lung MnSOD mRNA occurred promptly (4 h), with or without hyperoxic exposure. In parallel, lung MnSOD protein and activity were increased after 24 h, and protein levels remained elevated after 52 h. MnSOD activity and protein levels were closely correlated. Neither lung copper-zinc superoxide dismutase (CuZnSOD) mRNA nor activity increased following administration of cytokines. Small increases in CuZnSOD mRNA, which did not exceed those in beta-actin mRNA, occurred early (4 h) after endotoxin, but CuZnSOD activity was unchanged. Immunohistochemistry was used to demonstrate in which cell types the increase in MnSOD protein occurred after cytokine or endotoxin administration. In agreement with ELISA findings, immunoreactive MnSOD appeared to be increased in lung parenchyma, but not in lung neutrophils, 24 h after cytokine or endotoxin treatment. MnSOD was heavily concentrated in alveolar type II cells. However, the numbers of surfactant protein D-positive (type II) cells in lung sections did not appear to be increased after treatment with cytokines or endotoxin. We conclude that early and sustained increases in endogenous MnSOD, but not CuZnSOD or other antioxidant enzymes, are associated with protection of rat lungs against hyperoxic damage by cytokines or endotoxin.
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PMID:Lung manganese superoxide dismutase increases during cytokine-mediated protection against pulmonary oxygen toxicity in rats. 811 Apr 68

The model of toxic liver injury was used to examine the role of manganese superoxide dismutase (MnSOD) expression in cellular resistance to tumor necrosis factor (TNF)-alpha toxicity. The effects of the hepatotoxin D-galactosamine (GalN) and lipopolysaccharide (LPS) on hepatic and splenic TNF-alpha and MnSOD expression were studied. Treatment with GalN and LPS alone or in combination led to equivalent increases in hepatic and splenic TNF-alpha gene expression. Hepatic MnSOD mRNA levels were not affected by GalN or GalN with LPS but were increased 13-fold by LPS alone. Splenic MnSOD mRNA levels were increased twofold by GalN and 12-fold by either LPS alone or GalN plus LPS. The determination of MnSOD protein content, however, revealed no changes in hepatic or splenic steady-state levels of the protein with any of the treatments, despite the marked increases in MnSOD gene expression. Hepatic MnSOD enzyme activity was also unchanged by LPS or GalN plus LPS administration. Biosynthesis of MnSOD protein in rat hepatocytes isolated from an in vivo LPS-treated rat was unchanged compared with control. MnSOD mRNA levels were increased when GalN treatment was combined with uridine rescue, but again no change in protein was seen. The lack of any increase in MnSOD protein after GalN or LPS administration indicates that MnSOD upregulation is not involved in cellular resistance against TNF-alpha cytotoxicity in the liver in vivo.
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PMID:Induction of MnSOD gene expression in a hepatic model of TNF-alpha toxicity does not result in increased protein. 817 9

Intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 50 micrograms/kg increased the activity and the mRNA level of manganese superoxide dismutase (Mn-SOD) but did not change those of copper/zinc-SOD (Cu/Zn-SOD) in the rat pancreas. Both the formation of pancreatic edema and the elevation of serum amylase during caerulein pancreatitis were significantly relieved in the rats pretreated with LPS (50 micrograms/kg) compared with the rats without the pretreatment. These results support the view that superoxides play a key role in the pathogenesis of caerulein pancreatitis, and that Mn-SOD in the pancreas may work as a defense against the development of this disease.
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PMID:Lipopolysaccharide induces manganese superoxide dismutase in the rat pancreas: its role in caerulein pancreatitis. 855 79

Bidirectional communication occurs between neuroendocrine and immune systems through the action of various cytokines. Responses to various inflammatory mediators include increases in intracellular reactive oxygen species (ROS), notably, superoxide anion (O2-) and nitric oxide (NO.). Neurotoxicity mediated by NO. may result from the reaction of NO. with O2, leading to formation of peroxynitrite (ONOO-). ROS are highly toxic, potentially contributing to extensive neuronal damage. We, therefore, evaluated the effects of a variety of inflammatory mediators on the regulation of mRNA levels for manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS) in primary cultures of rat neuronal and glial cells. To determine age-dependent variation of mRNA expression, we used glial cells derived from newborn, 3-, 21-, and 95-day-old rat brains. Interleukin-1 beta, interferon-gamma (IFN-gamma), bacterial lipopolysaccharide (LPS), and tumor necrosis factor-alpha showed significant induction of MnSOD in both glial and neuronal cells. However, only LPS and IFN-gamma increased iNOS mRNA. These data demonstrate that these two genes are similarly regulated in two cells of the nervous system, further suggesting that the oxidative state of a cell may dictate a neurotoxic or neuroprotective outcome.
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PMID:Regulation of the manganese superoxide dismutase and inducible nitric oxide synthase gene in rat neuronal and glial cells. 878 45

Cultured rat vascular smooth muscle cells (VSMCs) produce nitric oxide (NO) under stimulation by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). NO synthase (NOS) and manganese superoxide dismutase (Mn-SOD) mRNA expressions are simultaneously induced by these stimulants in rat VSMCs. In VSMCs, S-nitroso-N-acetyl penicillamine (SNAP), one of the NO releasing reagents, induces Mn-SOD mRNA which may protect the VSMCs themselves. This suggests that NO itself may enhance the expression of Mn-SOD to protect the VSMC themselves against NO radicals in cultured rat VSMCs.
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PMID:Nitric oxide releasing reagent, S-nitroso-N-acetylpenicillamine, enhances the expression of manganese superoxide dismutase mRNA in rat vascular smooth muscle cells. 883 75


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