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

To determine whether heme oxygenase-1 (HO-1) protein is induced by endogenous nitric oxide (NO) in rat glial cultures, we examined the effects of lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and NO donors such as S-nitroso-N-acetylpenicillamine (SNAP), in mixed glial cells and in vivo rat hippocampus. In cultured glial cells, treatment with LPS induced the expression of 130-kd inducible NO synthase (iNOS) after 6 h, and NO2- accumulation and enhancement of the protein level of 33-kd HO-1 after 12 h. In addition, treatment with SNAP induced HO-1 expression after 6 h. Although NOS inhibitors such as NG-nitro-L-arginine (NNA) and NG-methyl-L-arginine did not change LPS-induced iNOS expression, these inhibitors suppressed both NO2- accumulation and the enhancement of HO-1. Immunocytochemistry showed that treatment with LPS for 24 h induced iNOS immunoreactivity predominantly in ameboid microglia, while this treatment induced HO-1-immunoreactivity in both microglia and astrocytes. In in vivo rat hippocampus, microinjection of LPS plus IFN-gamma, or SNAP after 24 h also induced HO-1 immunoreactivity in reactive microglia and astrocytes. In addition, intraperitoneal administration of NNA inhibited HO-1 immunoreactivity induced by the microinjection of LPS plus IFN-gamma. These results suggest that endogenous NO production by iNOS in microglia causes autocrine and paracrine induction of HO-1 protein in microglia and astrocytes in vitro and in rat brain.
 ...
PMID:In vitro and in vivo induction of heme oxygenase-1 in rat glial cells: possible involvement of nitric oxide production from inducible nitric oxide synthase. 953 34

Recent studies have indicated that glial cells such as astrocytes and microglia are activated in an early and delayed episode after brain damage. However, the mechanism and function of glial activation are still unclear. I examined whether the induction of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1) and major histocompatibility complex (MHC) antigen was involved in the glial activation. The microinjection of interferon-gamma and lipopolysaccharide into rat hippocampus induced MHC class II and iNOS in microglia. The iNOS induction may be involved in the activation of tyrosine kinases and transcription factors such as signal transducer and activator of transcription-1 (STAT1) and nuclear factor-kappa B (NF-kappa B). Subsequently, neuronal cell death occurred in the hippocampus, but cell death was undetectable in both microglia and astrocytes that expressed HO-1. Thus, induction of iNOS and HO-1 in glial cells may be involved in hippocampal neurodegeneration and resistance to oxidative stress in glial cells, respectively. In Alzheimer's disease (AD) brains, iNOS expression was at a very low level, although STAT1 and NF-kappa B were significantly increased. Also, Bcl-2, Bcl-x, Bak, Bad and p53 were increased in AD brains. These observations suggest that oxidative stress and glial activation without iNOS induction may be involved in neurodegeneration of AD brains.
 ...
PMID:[Functional activation of glial cells in early and delayed episodes of the brain damage]. 958 78

Recent observations suggest a possible interaction between the nitric oxide (NO)/NO synthases and carbon monoxide (CO)/heme oxygenases systems. We examined the effects of lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and NO donor such as S-nitroso-N-acetylpenicillamine (SNAP) on induction of inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) in mixed glial cells and in rat hippocampus. In in vitro glial cells, treatment with LPS induced the expression of 130-kDa iNOS after 6 h, and NO2- accumulation and enhancement of the protein level of 33-kDa HO-1 after 12 h. In addition, treatment with SNAP induced HO-1 expression after 6 h. Although a NOS inhibitor, such as N(G)-nitro-L-arginine (NNA), did not change LPS-induced iNOS expression, the inhibitor suppressed both NO2- accumulation and the enhancement of HO-1. Immunocytochemistry showed that LPS-treatment induced iNOS-immunoreactivity predominantly in microglia, while this treatment induced HO-1-immunoreactivity in both microglia and astrocytes. These results suggest that endogenous NO production by iNOS in microglia causes autocrine- and paracrine-induction of HO-1 protein in microglia and astrocytes in rat brain.
 ...
PMID:Induction of inducible nitric oxide synthase and heme oxygenase-1 in rat glial cells. 958 63

The expression of heat shock proteins (HSPs) as stress-induced proteins was studied in mice injected with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) as an experimental endotoxic shock model. The expression of constitutive type heat shock protein 70 (HSC70) was significantly reduced in livers of mice injected with D-galactosamine and lipopolysaccharide, while its expression was unaffected in livers of mice injected with D-galactosamine or lipopolysaccharide alone. The expression of other constitutive type heat shock proteins, namely HSP60, HSP32 and HSP25 was also reduced in mice injected with D-galactosamine and lipopolysaccharide. On the other hand, inducible type HSP70 was detected in livers from mice injected with D-galactosamine and lipopolysaccharide, but not in livers from mice injected with D-galactosamine or lipopolysaccharide alone. Simultaneous injection of anti-tumor necrosis factor (TNF)-alpha antibody prevented the liver from reduced expression of constitutive type HSC70, and lead to marked expression of inducible type HSP70 in the liver. Reduced expression of constitutive type HSC70 was also found when D-galactosamine and recombinant TNF-alpha was injected. Therefore, TNF-alpha was suggested to play a critical role on altered expression of constitutive HSC70 and inducible type HSP70 in response of D-galactosamine-sensitized mice to lipopolysaccharide.
 ...
PMID:Altered expression of constitutive type and inducible type heat shock proteins in response of D-galactosamine-sensitized mice to lipopolysaccharide as an experimental endotoxic shock model. 965 19

Our group recently reported that cultured sheep pulmonary artery endothelial cells (SPAECs) became resistant to lipopolysaccharide (LPS)-induced apoptosis several days after constitutive synthesis of nitric oxide (NO) after adenoviral (Ad) transfer of inducible NO synthase (iNOS) or exposure to the NO donor S-nitroso-N-acetylpenicillamine (SNAP) (E. Tzeng, Y.-M. Kim, B. R. Pitt, A. Lizonova, I. Kovesdi, and T. R. Billiar. Surgery 122: 255-263, 1997). In the present study, we confirmed this observation by establishing stable transfectants after retroviral gene transfer [replication-deficient retrovirus (DFG)] of human iNOS (DFG-iNOS) SPAECs and then used all three approaches (Ad, DFG, and SNAP) to determine underlying mechanisms of this phenomenon. Continuous endogenous production of NO in itself did not cause apoptosis as assessed by phase-contrast microscopy, nuclear morphology, and internucleosomal DNA fragmentation. Prolonged (72-96 h) synthesis of NO, however, after DFG- or replication-deficient adenovirus (Ad. CMV)-iNOS or SNAP (100 microM, 96 h) inhibited LPS-induced apoptosis. The kinetics of such protection suggested that NO may be inducing other gene products. Ad-mediated transfer of manganese superoxide dismutase (MnSOD) decreased the sensitivity of wild-type SPAECs to LPS-induced apoptosis. MnSOD, however, was not induced in an NG-monomethyl-L-arginine (L-NMMA)-sensitive time-dependent fashion after Ad.CMV-iNOS. Other inducible genes that may be affected by NO and that may protect against potential oxidant-mediated LPS-induced apoptosis including 70-kDa heat shock protein, heme oxygenase-1, metallothionein, and Bcl-2 also were not elevated in an L-NMMA-sensitive, time-dependent fashion. Although the candidate gene product underlying NO-induced protection remains unclear, we did note that prolonged synthesis of NO inhibited LPS-induced activation of an interleukin-1beta-converting enzyme-like cysteine protease (cysteine protease protein-32-like) in a dithiothreitol-sensitive fashion, suggesting that S-nitrosylation of an important downstream target of convergence of apoptotic signals may contribute to the sensitivity of SPAECs to LPS.
 ...
PMID:Nitric oxide inhibits lipopolysaccharide-induced apoptosis in pulmonary artery endothelial cells. 975 4

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by 15-deoxy-delta(12,14) prostaglandin J2 (15d-PGJ2), anti-diabetic thiazolidinediones and several non-steroidal anti-inflammatory drugs (NSAIDs). In rat glial cells, lipopolysaccharide and interferon-gamma (LPS/IFN-gamma) induced expression of both inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). PPARgamma activators inhibited iNOS expression by LPS and IFN-gamma. However, PPARgamma activator alone induced HO-1 expression and further enhanced LPS/IFN-gamma-induced HO-1 expression. These results suggest that activation of PPARgamma negatively regulate iNOS expression and positively regulates HO-1 expression in glial cells.
 ...
PMID:Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit inducible nitric oxide synthase expression but increase heme oxygenase-1 expression in rat glial cells. 1020 48

Septic shock induced by lipopolysaccharide (LPS) produces systemic hypotension and decreased responsiveness to vasoconstrictors. Recently, intravenous injection of hemoglobin (HGB) into rats was found to be protective from a subsequent lethal dose of LPS and was correlated with induction of the enzyme heme oxygenase-1 (HO-1). To determine whether the HGB modulated the vasomotor tone of systemic arteries, we evaluated the effect of in vivo treatment with HGB and LPS on vasoconstrictor responses to phenylephrine (PE) in the isolated rat aorta. Rats (n = 4, for each group) were injected intravenously with rat HGB (200 mg/kg i.v.) or normal saline control (CON) 16 h before sacrifice, and/or LPS (20 mg/kg) or CON 4 h before sacrifice. The descending aorta was dissected into rings and suspended in a modified Krebs solution where vasoconstrictor responses were determined to KCl (60 mM) and PE (10(-8) to 10(-5) M). LPS, but not HGB, inhibited the vasoconstrictor response to KCl. LPS, HGB, and HGB+LPS inhibited the maximal vasoconstrictor response to PE (PEmax). Induction of HO-1 RNA in the aorta by HGB and by LPS was demonstrated by Northern blot analysis. To determine if induction of HO-1 was related to the effect of LPS or HGB on vascular reactivity, vessels were treated with the HO-1 inhibitor, SnPP9 (30 microM). PEmax in SnPP9+HGB vessels was not different from control, whereas SnPP9+LPS vessels had a marked decrease in PEmax. We conclude that induction of HO-1 does not protect the rat aorta from the vasodepressor effects of LPS in vitro. Our results demonstrate, however, that the induction of HO-1 causes vasodepression, possibly via increased production of carbon monoxide.
 ...
PMID:Induction of heme oxygenase-1 with hemoglobin depresses vasoreactivity in rat aorta. 1021 6

Heme-binding protein 23 (HBP23) is a cytosolic protein that binds the prooxidant heme with high affinity and has been implicated in the cellular protection against reactive oxygen species (ROS). Because lipopolysaccharide (LPS) stimulates macrophages to produce large amounts of ROS the gene expression of HBP23 was analyzed during treatment with LPS in cultured rat Kupffer cells (KC). HBP23 was constitutively expressed in KC and up-regulated on the protein and messenger RNA (mRNA) level by LPS with a time response distinct from that of TNFalpha, but in coordination with that of heme oxygenase-1 (HO-1), which is the inducible isoform of the rate-limiting enzyme of heme degradation. A parallel up-regulation of HBP23 and HO-1 mRNA by LPS was also observed in cultured peritoneal macrophages and peripheral blood monocytes. HBP23 mRNA induction by LPS occurred on the transcriptional level as indicated by blocking with actinomycin D. The induction of HBP23 mRNA expression by LPS was preceded by that of the inducible nitric oxide synthase (iNOS) and the production of nitrite in KC. Treatment with the NOS inhibitor NG-monomethyl L-arginine prevented HBP23 mRNA induction by LPS, which was reversed by an excess of L-arginine. Both the nitric oxide (NO)-donor S-nitroso-N-acetylpenicillamine and the peroxynitrite donor SIN-1 increased HBP23 mRNA expression. HBP23 mRNA induction by LPS was down-regulated by interleukin 10 and transforming growth factor beta1 with a NO-independent mechanism. LPS-stimulated KC exhibited marked protection against the cytotoxicity mediated by H2O2. The data suggest that NO and peroxynitrite are major mediators of the LPS-dependent up-regulation of HBP23 in KC.
 ...
PMID:Up-regulation of heme-binding protein 23 (HBP23) gene expression by lipopolysaccharide is mediated via a nitric oxide-dependent signaling pathway in rat Kupffer cells. 1038 47

We previously reported (Arch. Toxcol. 1998, 72, 492-498) that the differential decrease in the levels of hepatic cytochrome P450 (CYP) isozymes in rats was observed 24 hr after intracerebroventricular (i.c.v.) injection of bacterial lipopolysaccharide (LPS) at the dose ineffective (0.1 microgram) when injected intraperitoneally (i.p.). Among CYP isozymes we examined, the male specific CYP isozyme, CYP2C11 was most severely affected by i.c.v. injection of LPS. In this study, we examined the gene expression of CYP2C11, the total P450 contents, the CYP2C11-dependent activity of imipramine N-demethylase (IMND) and protein of CYP2C11 10 hr after i.c.v. or i.p. injections of LPS. Intracerebroventricular injection of LPS significantly decreased the level of CYP2C11 mRNA (to 63% of saline i.c.v. control), the total P450 contents (to 70% of saline i.c.v. control), the IMND activity (to 74% of saline i.c.v. control), but not protein of CYP2C11 in rat liver. In contrast, i.p. injection of LPS at the same dose as i.c.v. did not significantly affect these parameters. Since CYP is a heme protein, we also measured the activity of heme oxygenase (HO) using the same rat liver microsomes. The HO activity was increased to 166% by i.c.v. injection of LPS and 135% by i.p. injection of LPS compared to corresponding saline control. It is suggested that i.c.v. injection of LPS down-regulates the expression of CYP2C11 at transcriptional level and that both the decrease in CYP2C11 mRNA and the increase in heme degradation may be involved in the decreased level of protein and activity of CYP2C11 by i.c.v. injection of LPS in rat liver.
 ...
PMID:Decrease in hepatic CYP2C11 mRNA and increase in heme oxygenase activity after intracerebroventricular injection of bacterial endotoxin. 1042 81

Heme oxygenase catalyzes the metabolism of heme to biliverdin, free iron, and carbon monoxide (CO), which has been shown to be an important neuromodulatory agent. Recently, it has been demonstrated that lipopolysaccharide (LPS) can induce the enzyme heme oxygenase in glial cells. Therefore, the present study was designed to test the hypothesis that central CO plays a role in LPS-induced fever. Colonic body temperature (T(b)) was measured in awake, unrestrained rats (basal T(b) = 36.8 +/- 0.2 degrees C). Intracerebroventricular injection of zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 75 nmol), a heme oxygenase inhibitor, caused no significant change in T(b), indicating that the central heme oxygenase pathway plays no tonic role in T(b) under the experimental conditions used. Intraperitoneal injections of LPS (50-100 microgram/kg) evoked dose-dependent increases in T(b). Intracerebroventricular injection of ZnDPBG in febrile rats attenuated LPS-induced fever (thermal index with ZnDPBG = 1.1 +/- 0. 2 degrees C, thermal index with vehicle = 2.3 +/- 0.4 degrees C), suggesting that the central heme oxygenase pathway plays a role in fever generation. The antipyretic effect of ZnDPBG could be reversed by intracerebroventricular administration of heme-lysinate or CO-saturated saline. Collectively, our data indicate that CO arising from heme oxygenase may play an important role in fever generation by acting on the central nervous system.
 ...
PMID:Carbon monoxide as a novel mediator of the febrile response in the central nervous system. 1044 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>