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)

In situ hybridization and Northern analysis of heme oxygenase (HO) mRNA was used to determine the induction and expression of HO by various environmental agents. Exposure of Hep3B cells to hemin (10 microM) for as little as 5 min resulted in significant production of HO transcripts and mRNA expression as seen by in situ hybridization. We followed the pattern of HO transcript accumulation by heme and results indicate that the peak of induction of HO by heme was reached between 10 and 20 minutes. Other metalloporphyrins were all effective in inducing HO mRNA after 1 h exposure. On the other hand, CoCl2 caused accumulation of HO mRNA at a later time than seen with the metalloporphyrins. However, lipopolysaccharide (LPS) gave a more immediate effect on HO induction which was somewhat similar to heme in its time course. Direct measurements of HO activity revealed that enzyme activity could be detected after about 20 min exposure to hemin, and this activity was inhibited by tin protoporphyrin (SnPP). The different pattern of HO mRNA induction by LPS as contrasted with CoCl2 suggests that LPS may act through a different translational factor, or stimulate free radical formation and the subsequent release of heme and induction of HO. These results indicate that heme causes accumulation of HO mRNA by a different mechanism than that of CoCl2. Finally, LPS shares a concomitant effect on induction of HO as an acute phase reactant type protein.
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PMID:Differential induction of heme oxygenase in the hepatocarcinoma cell line (Hep3B) by environmental agents. 132 19

The possible role for adrenergic influences or prostaglandins in the effects of endotoxin to inhibit the glucocorticoid induction of hepatic tryptophan oxygenase (TO) activity, to decrease the hepatic microsomal cytochrome P--450-dependent drug-metabolizing activity, and to induce heme oxygenase activity was examined. Administration of the alpha-adrenergic locking agents phenoxybenzamine or phentolamine attenuated the inhibitory effect of the bacterial lipopolysaccharide on the induction of TO activity by dexamethasone. Injection of a beta-adrenergic blocker, propranolol, or of indomethacin, an inhibitor of prostaglandin biosynthesis, accentuated the effect of endotoxin to inhibit TO induction. Neither phenoxybenzamine, propranolol, nor indomethacin altered the effect of endotoxin to decrease aniline hydroxylase activity, ethylmorphine N-demethylase activity, or the levels of cytochrome P--450. Also, dexamethasone administration did not significantly protect against the effects of endotoxin on the hepatic microsomal drug metabolizing enzyme system, and none of the pharmacological agents diminished the effects of endotoxin to induce hepatic heme oxygenase activity. Endotoxin administration was also shown to diminish, but not prevent, the induction of cytochrome P--450 and ethylmorphine N-demethylase activity produced by phenobarbital. The results indicate that alpha-adrenergic mechanisms are involved in the endotoxic inhibition of the glucocorticoid induction of TO activity and suggest that neither adrenergic influences nor prostaglandins play a significant role in the effect of endotoxin to decrease hepatic mixed-function oxidase activity.
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PMID:Investigation of adrenergic and prostaglandin influences in the endotoxin alteration of hepatic heme oxygenase, microsomal mixed-function oxidase, and glucocorticoid-induced tryptophan oxygenase activities. 613 93

Two mechanisms contribute to cGMP formation by soluble guanylyl cyclase (i) NO production by NO synthase and (ii) CO production by heme oxygenase. We analyze here the contributions of these two pathways to IL1, TNF, lipopolysaccharide and hemin treated brain capillary endothelial cells. Cytokines and LPS induced cGMP formation in manners that were completely prevented by LY 83,583, methylene blue and by cyclosporin A. They were partially inhibited by inhibitor of NO synthase. Cyclosporin A acts by a posttranscriptional mechanism. Cells constitutively expressed mRNAs for heme oxygenase-1. Expression was enhanced by hemin but not by IL1 or lipopolysaccharide. Induction of heme oxygenase-1 and its inhibition by Sn protoporphyrin IX had no effect on cGMP levels.
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PMID:Contributions of NO synthase and heme oxygenase to cGMP formation by cytokine and hemin treated brain capillary endothelial cells. 754 88

We examined the possibility that bilirubin physiologically acts as an antioxidant by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide: LPS). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. The LPS injection markedly increased bilirubin oxidative metabolites in urine of rats fed an ascorbic acid-free diet. This increase was supressed by feeding an adequate amount of ascorbic acid, a physiological antioxidant. the concentrations of biotripyrrin-a and -b in urine collected 6.5-10 h after the LPS injection were lower in rats fed an ascorbic acid-supplemented diet than in rats fed an ascorbic acid-free diet. Moreover, feeding with ascorbic acid suppressed the elevation of hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with LPS. These findings suggest that bilirubin is oxidized in rats treated with LPS and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.
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PMID:Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo. 766 30

Interleukin-2 (15 micrograms/mouse, i.p. twice daily for 4 days and once on the 5th day) significantly lowered cytochrome P-450 and heme content and increased heme oxygenase mRNA accumulation; the activities of 7-ethoxycoumarin O-deethylase, ethoxy- and pentoxyphenoxazone O-dealkylases were decreased. The activity of the type O form of hepatic xanthine oxidase increased, but there was no increase in lipid peroxide, expressed in terms of microsomal malondialdehyde. In vivo inactivation of xanthine oxidase activity by feeding mice with tungstate did not substantially change the degree of interleukin-2-induced cytochrome P-450 depression, suggesting that the two processes are not causally linked. Induction of tolerance to endotoxin by a 4-day pretreatment with lipopolysaccharide resulted in 50% protection against this depression despite inhibition of the interleukin-2 induced formation of tumor necrosis factor. This suggests that the release of tumor necrosis factor per se does not fully account for the depression of cytochrome P-450. Dexamethasone, already used in patients to reduce the toxicity of interleukin-2 therapy, provided full protection against the cytochrome P-450 depression.
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PMID:Mechanisms of interleukin-2-induced depression of hepatic cytochrome P-450 in mice. 779 64

We have examined the role of soluble guanylyl cyclase and possible mediators of its activation in the vascular hyporeactivity caused by bacterial endotoxin (lipopolysaccharide, LPS) ex vivo. Treatment of rats with E. coli LPS (10 mg/kg, i.v. for 3h) resulted in a significant reduction in the contractions elicited by norepinephrine (NE; 10(-9)-10(-6) M) in endothelium-denuded aortic rings ex vivo. Methylene blue or LY-83583, inhibitors of soluble guanylyl cyclase, completely restored contractions to NE, whereas the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), caused only a partial restoration. Zinc protoporphyrin-IX, an inhibitor of heme oxygenase, did not enhance NE-induced contraction in rings from LPS-treated rats, indicating that the production of carbon monoxide (CO) does not contribute to this vascular hyporeactivity. Indomethacin, an inhibitor of cyclooxygenase, further suppressed the contractions in rings from LPS-treated rats. These results suggest that hyporesponsiveness to NE caused by LPS is due to the activation of soluble guanylyl cyclase, which is partially mediated by N(O), but not by CO. Moreover, LPS may induce the production of another mediator(s) that activate soluble guanylyl cyclase in the vascular smooth muscle.
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PMID:Activation of soluble guanylyl cyclase by a factor other than nitric oxide or carbon monoxide contributes to the vascular hyporeactivity to vasoconstrictor agents in the aorta of rats treated with endotoxin. 791 Oct 15

The synthesis of 23 kDa protein was enhanced when mouse peritoneal macrophages were exposed to oxidative agents such as hydrogen peroxide and menadione, or to sulfhydryl-reactive agents such as diethylmaleate, cadmium chloride and sodium arsenite. After 11 h exposure to these agents the 23 kDa protein was one of the actively synthesized proteins in the macrophages. Under similar conditions the 34 kDa protein previously identified as heme oxygenase, was induced and its synthesis preceded that of the 23 kDa protein. Neither the 23 kDa or the 34 kDa protein was induced by hyperthermia. Conversely, the various oxidative and sulfhydryl-reactive agents employed here did not induce the major heat shock proteins in the macrophages. When the macrophages were activated by bacterial lipopolysaccharide or other stimulants, many proteins are known to be induced, however, the 23 kDa and 34 kDa proteins were not induced. The 34 kDa protein, i.e., heme oxygenase, has been found to be stress-induced in various types of cell, but not the 23 kDa protein. This suggests that the 23 kDa protein is a stress protein predominantly expressed in macrophages.
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PMID:Induction of a 23 kDa stress protein by oxidative and sulfhydryl-reactive agents in mouse peritoneal macrophages. 849 60

Astroglial cells are resistant to cell death and morphologic damage following lead (Pb) exposure at concentrations which elicit detrimental effects in neurons. A possible explanation may be that astroglial cells respond to Pb by increasing the expression of specific proteins, such as heat-shock proteins (HSPs), which confer resistance to low levels of Pb. However, there has been relatively limited information regarding the ability of Pb to evoke the synthesis of HSPs. In the current study, pulse-labeling of cultured astroglial proteins with [3H]-leucine was used to evaluate the nature of Pb-induced changes in protein expression. The effect of Pb on newly synthesized proteins was compared to the response elicited by heat-shock and oxidative injury. Immunoblot analysis was utilized to examine alterations in levels of various stress proteins including HSP27, HSP70, HSP90, and heme oxygenase-1 (HO-1). Even though Pb induced the synthesis of proteins with estimated molecular weights of 23 kDa, 32 kDa, 70 kDa, and 90 kDa, the accumulation of HSPs other than HO-1 was not observed. Hyperthermia and treatment with Na arsenite both resulted in enhanced expression of HSP70 and HO-1. In addition, exposure to hydrogen peroxide (H2O2), cadmium (Cd), and lipopolysaccharide (LPS) stimulated a rise in HO-1 levels. Although cellular insult failed to elicit an increase in either HSP27 or HSP90, cultured astroglia expressed readily detectable levels of both these proteins. Furthermore, Pb exposure resulted in the development of crosstolerance to subsequent injury by treatment with either Cd or H2O2. The results of this study indicate that Pb triggers a less conventional stress response in astroglial cells, which may provide enhanced resistance to the toxic effects of Pb.
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PMID:Relationship of lead-induced proteins to stress response proteins in astroglial cells. 860 Feb 94

We investigated the effect of nitric oxide (NO) on the induction of the stress protein heme oxygenase and its protective role in vascular endothelial cells exposed to hydrogen peroxide. Treatment of porcine aortic endothelial cells for 6 h with the NO-releasing compounds (0.1-1 mM) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) resulted in a concentration-dependent increase in heme oxygenase activity. At 1 mM, the activity of heme oxygenase was augmented 8.5-fold with SNP, 5.8-fold with SNAP, and 5.7-fold with SIN-1 over the control value. In contrast, endothelial cells exposed to 100 microM S-bromoguanosine 3',5'-cyclic monophosphate, a tissue-permeable analogue that mimics the action of guanosine 3',5'-cyclic monophosphate, did not show any change in heme oxygenase activity. Activation of the inducible NO synthase by the synergistic action of bacterial lipopolysaccharide (250 ng/ml) and interferon-gamma (100 U/ml) also increased endothelial heme oxygenase activity by 3.2-fold (P < 0.05 vs control). Methylene blue (1 microM), an inhibitor of both NO synthase and guanylate cyclase activities, completely abolished this effect. Cells previously exposed to SNAP and SIN-1 exhibited a significant protection against the cytotoxicity mediated by hydrogen peroxide (250 microM) (P < 0.05). Conversely, SNP did not show any protective effects, possibly because of catalytic iron released during its chemical decomposition. In fact, the iron chelator deferoxamine (5 mM) completely suppressed the SNP-mediated cytotoxicity and partially attenuated the activity of heme oxygenase to a level equal to that mediated by SIN-1 and SNAP. These results indicate that NO is a determinant in the modulation of the activity of heme oxygenase leading to a major resistance of the endothelium to oxidative stress.
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PMID:NO-mediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium. 876 40

It has been known for a long time that heme oxygenase (HO) is a key enzyme in heme catabolism, and it was found to act as an oxidative-stress protein to produce carbon monoxide, which has similar actions to those of nitrogen monoxide. We examined transcriptional control of the HO gene in mouse M1 (myeloleukemia) cells during treatment with lipopolysaccharide (LPS; an oxidative reagent). Since the promoter region of this gene in human cells contains a 12-O-tetradecanoyl- phorbol-13-acetate(TPA)-responsive element (TRE) and a nuclear-factor-kappa B-responsive element. HO mRNA expression might be regulated by an oxidative activation pathway. We investigated activation of the HO gene after treatment of M1 cells with LPS. Upon treatment with LPS, H2O2 was produced, the nuclear proto-oncogenes fos and jun were activated, then the HO gene was activated. The extent of transcriptional activation of the fos, jun and HO genes in M1 cells treated with LPS was strongly reduced by a scavenger of oxygen radicals (N-acetyl-L-cysteine), but a specific inhibitor of protein kinase C only reduced transcriptional activation by 10-20%. These results suggest that LPS may be an oxidative reagent. Some oxidative reagents (e.g., H2O2) are strong activators of NF-kappa B, and therefore we treated M1 cells with H2O2. Essentially the same extends of transcriptional activation of the fos, jun and HO genes were observed as those observed after LPS treatment. Super-shift assays with DNA that contained the TRE motif revealed that the Fos and Jun proteins from nuclei of M1 cells treated with LPS and H2O2 bound weakly to the TRE motif, and, in assays with DNA that contained the NF-kappa B motif, nuclear protein from M1 cells treated with H2O2 or LPS bound strongly to the NF-kappa B motif. These results strongly suggest that the HO gene in M1 cells is mainly activated by LPS through oxidative activation of NF-kappa B due to production of H2O2.
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PMID:Lipopolysaccharide activates transcription of the heme oxygenase gene in mouse M1 cells through oxidative activation of nuclear factor kappa B. 877 98


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