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)

Cytogenetic analyses were performed on cells from 17 patients with hairy cell leukemia stimulated with polyclonal B-cell activators (in 155 different cultures). No mitosis was obtained in samples from four cases (23.5%). Of 14 bone marrows, four (28.6%) showed mitoses, two with clonal abnormalities. All four samples from the spleen had mitoses with four clonal changes; eight of 13 (37.5%) blood samples had mitoses with three clonal changes. Of the polyclonal B-cell activators (PBA), lipopolysaccharide and protein A seemed to be effective for the detection of clonal abnormalities in hairy cell leukemia. Among the clonal aberrations, chromosomes #3, #10, and #17 were affected in two cases each; frequent numerical changes were monosomies of #10 and #17 and structural changes were deletions at band 3p21 (two cases), 6q-, and der(9)t(9;?)(p22;?). The chromosomal bands involved in structural changes were close to accepted constitutive fragile sites.
 ...
PMID:Cytogenetic studies in hairy cell leukemia. 349 70

Using oligomer primers based on the cDNA sequence of human interleukin 1 beta converting enzyme (ICE), we have employed the RT-PCR method and rat spleen RNA to clone and sequence rat ICE. We report here that the predicted amino acid sequence of rat ICE proenzyme consists of 402 amino acids (p45) and shares 61% and 90% identity, respectively, with human and mouse ICE amino acid sequences. The active site cysteine (Cys284) and 3 or 3 potential processing sites are conserved suggesting that their the rat ICE heterodimer consists of a p22 (Ser104-Asp296) and a p10 (Gly315-His402) subunit or a cryptic processing site creates a smaller heterodimer. Northern blot analysis has revealed a approximately 2.2 kb and a more abundant approximately 1.45 kb ICE transcript both widely expressed in the rat with the highest expression in spleen and intestine and lowest in brain. IL-1 beta mRNA was similarly distributed. Injection of the immunostimulant, lipopolysaccharide (0.2 mg/kg, i.p.), increased rICE mRNA content between 2- to 3-fold in the rat brain with smaller increases measured in testis and spleen. The structural conservation of this enzyme suggests that rat models of inflammation will be useful for evaluating the therapeutic potential of ICE inhibitors in humans.
 ...
PMID:Cloning, tissue expression and regulation of rat interleukin 1 beta converting enzyme. 778 29

Recently, we showed that cultured guinea pig gastric pit cells possess a phagocyte NADPH oxidase-like activity, which was up-regulated by Helicobacter pylori lipopolysaccharide. We demonstrate here that these cells express all of the phagocyte NADPH oxidase components (gp91-, p22-, p67-, p47-, and p40-phoxes). Treatment with lipopolysaccharide increased the expression of gp91-, p22-, and p67-phoxes, but not that of p47- and p40-phoxes. Intriguingly, the p67-phox expression consistently correlated with up-regulation of superoxide anion-producing ability. Thus, the gastric pit cell NADPH oxidase may play an important role in regulation of the inflammatory response associated with H. pylori infection.
 ...
PMID:Helicobacter pylori lipopolysaccharide enhances the expression of NADPH oxidase components in cultured guinea pig gastric mucosal cells. 1038 99

Gastric pit cells express mitogen oxidase1 (Mox1) and essential components for the phagocyte NADPH oxidase (p67-, p47-, p40-, and p22-phoxes). Helicobacter pylori (Hp) lipopolysaccharide (LPS) is a potent up-regulator of the Mox 1 oxidase. In this study, we examined the expression levels of several key members of the Toll-like receptor (TLR) family in primary cultures of guinea pig gastric pit cells. These cells expressed the TLR4 mRNA. Immunoblot analysis and immunofluorescence histochemistry with an anti-TLR4 antibody showed that gastric pit cells possessed significant amounts of TLR4 protein preferentially on the plasma membrane. In contrast, the cells did not express the TLR2 and TLR9 transcripts and did not contain detectable amounts of TLR2 protein. Neither peptidoglycan from Staphylococcus aureus nor Hp DNA with the CpG motif up-regulated Mox1 oxidase activity. Hp LPS activated nuclear factor-kappa B in association with the expression of cyclooxygenase II and tumor necrosis factor alpha transcripts. These findings suggest that TLR4 may play a crucial role in the initiation of inflammatory responses of gastric pit cells against Hp infection.
 ...
PMID:Toll-like receptor 4 regulates gastric pit cell responses to Helicobacter pylori infection. 1169 59

The molecular sources of reactive oxygen species (ROS) in skeletal muscles are not well understood. We hypothesized that nonphagocyte NAD(P)H oxidase could be a source of ROS in muscle fibers. We thus investigated the existence, structure, and contribution of nonphagocyte NAD(P)H oxidase to ROS production in rat skeletal muscles. ROS production and NAD(P)H oxidase activity were evaluated by lucigenin-enhanced chemiluminescence and NADH consumption rate, whereas enzyme composition was monitored by reverse transcription-polymerase chain reaction and immunoblotting. Basal O(-)(2) production in muscle strips from normal rats averaged 1.4 nmol/mg per 10 min and increased to approximately 18 nmol/mg per 10 min in the presence of NADH. Muscle O(-)(2) production and NADH consumption were inhibited by Tiron, superoxide dismutase, apocynin, and diphenyleneiodonium but not by inhibitors of cyclo-oxygenases, xanthine oxidase, nitric oxide synthases (NOS), and mitochondrial enzymes. We detected mRNA and proteins of p22(phox), gp91(phox), p47(phox), and p67(phox) subunits in normal rat muscles. These subunits were localized in close proximity to the sarcolemma. Induction of sepsis in rats doubled muscle O(-)(2) production with no major changes in muscle NADPH oxide subunit expression. In lipopolysaccharide-treated but not in control muscles, O(-)(2) production was increased significantly by NOS inhibition. We conclude that a constitutively active NAD(P)H oxidase enzyme complex exists in normal skeletal muscle fibers and contributes to ROS production. In septic rats, this production is increased but measurable O(-)(2) is reduced by enhanced NO production.
 ...
PMID:Molecular characterization of a superoxide-generating NAD(P)H oxidase in the ventilatory muscles. 1255 34

Sepsis is associated with increased production of reactive oxygen species (ROS); however, the metabolic sources of increased ROS are not well understood. We hypothesized that the recently described nonphagocytic NAD(P)H oxidase system could be an important source of the ROS superoxide anion (O2-) during sepsis, and the interaction of O2- with nitric oxide (NO) may contribute to sepsis-induced vascular Injury. To evaluate this issue, we measured O2- production before and after treatment with lipopolysaccharide (LPS) in rats, who are Inducible NO synthase producers (NOSII) and in pigs, who do not produce NOSII. LPS increased O2- production in aorta from rats from 0.38 +/- 0.07 nmol/mg/10 min to 1.18 +/- 0.23 nmol/mg/10 min, (P = 0.001) in rats, and 0.63 +/- 0.05 nmol/mg/10 min to 1.5 +/- 1.6 nmol/mg/10 min (P = 0.001) in carotid arteries from pigs. Components of NAD(P)H oxidase, including p22(phox), gp91(phox), p47(phox), p67(phox), mRNA and p22(phox), and gp91(phox) proteins were present in rat aorta and aorta and carotid arteries from pigs. Expression mildly increased in rats, but not in pigs. In rats, NADH and NADPH greatly increased O2- production with no difference in untreated versus LPS-treated rats. The addition of L-NAME increased NADH-dependant O2- production from 75 +/- 3 nmol/O2-/mg/10 min to 113 +/- 7 nmoVO2-/mg/10 min in LPS-treated rats, but had no effect in untreated rats. In pigs, the NADH-stimulated O2- production was 43 +/- 8 nmol/mg/10 min before and 63 +/- 4.3 nmol/mg/10 min after LPS even without L-NAME (P < 0.05). In contrast to LPS-treated rats, L-NAME markedly decreased NADH-stimulated O2- production (63 +/- 4 nmol/mg/10 min to 33 +/- 5.6 nmol/mg/10 min, P < 0.01). Luminol-enhanced chemiluminescence was also Increased in porcine carotid arteries after LPS treatment, which is consistent with peroxynitrite formation. Our results indicate that components of NAD(P)H oxidase are present in vessels of pigs and rats and there is substantial NADH-dependent O2- production that is increased after LPS. However, the behavior of NAD(P)H oxidase in NOSII-producing and nonproducing species differs with a reduction of O2- by NO in rats and NO-dependent production in pigs.
 ...
PMID:Superoxide production in the vasculature of lipopolysaccharide-treated rats and pigs. 1274 95

Cyclooxygenase-2 (COX-2) is induced in response to lipopolysaccharide (LPS). However, the signaling mechanisms of LPS-induced COX-2 expression in cardiomyocytes are not well understood. The aim of this study was to investigate the role of gp91(phox)-containing NADH oxidase signaling pathway in LPS-induced COX-2 expression in cardiomyocytes. Cultured neonatal mouse cardiomyocytes showed basal COX-2 expression and PGE2 production. In response to LPS, COX-2 expression and PGE2 production increased by two- to four-fold, which were completely blocked by a selective COX-2 inhibitor NS398. LPS also increased NADH oxidase (gp91(phox) and p47(phox) subunits) expression and superoxide generation. Deficiency of gp91(phox) or suppression of p22(phox) expression decreased NADH oxidase activity and down-regulated COX-2 expression and PGE2 production stimulated by LPS. Pharmacological inhibitors of NADH oxidase prevented LPS-induced COX-2 expression and PGE2 production. The effect of NADH oxidase was mediated through MAPK activation, since inhibition of NADH-oxidase activity prevented phosphorylation of ERK1/2, p38, and JNK1/2, as well as selective inhibition of each subfamily of MAPK by siRNAs and a dominant negative mutant of JNK1 decreased COX-2 expression and completely abrogated PGE2 production in response to LPS. Furthermore, LPS-induced NF-kappaB activation was decreased by inhibition of NADH oxidase, ERK1/2 or JNK1/2 activation, suggesting that LPS increases NF-kappaB activity and COX-2 expression via NADH oxidase-dependent activation of ERK1/2 and JNK1/2. In conclusion, NADH oxidase signaling represents a novel pathway leading to COX-2 expression via MAPK/NF-kappaB-dependent mechanisms in cardiomyocytes during LPS stimulation. Our study suggests that gp91(phox)-containing NADH oxidase is a potential therapeutic target of sepsis.
 ...
PMID:NADH oxidase signaling induces cyclooxygenase-2 expression during lipopolysaccharide stimulation in cardiomyocytes. 1554 60

Ehrlichia chaffeensis is an obligate intracellular bacterium which replicates in monocytes or macrophages, the primary producers of reactive oxygen species (ROS). However, effects of ROS on E. chaffeensis infection and whether E. chaffeensis modulates ROS generation in host monocytes are unknown. Here, E. chaffeensis was shown to lose infectivity upon exposure to O(2)(-) or hydrogen peroxide. Upon incubation with human monocytes, E. chaffeensis neither induced O(2)(-) generation by human monocytes, nor colocalized with nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components. Instead, it actively blocked O(2)(-) generation by monocytes stimulated with phorbol myristate acetate and caused the rapid degradation of p22(phox), a component of NADPH oxidase. These effects were not seen in neutrophil, which is another potent ROS generator, but a cell type that E. chaffeensis does not infect. Trypsin pretreatment of monocytes prevented the inhibition of O(2)(-) generation by E. chaffeensis. The degradation of p22(phox) by E. chaffeensis was specific to subsets of monocytes with bound and/or intracellular bacteria, and the degradation could be reduced by heat treatment of the bacterium, lipopolysaccharide pretreatment of monocytes, or the incubation with haemin. The degradation of p22(phox) by E. chaffeensis and its prevention by haemin or protease inhibitors also occurred in isolated monocyte membrane fractions, indicating that host cytoplasmic signalling is not required for these processes. The amount of gp91(phox) was stable under all conditions examined in this study. These findings point to a unique survival mechanism of ROS-sensitive obligate intraleucocytic bacteria that involves the destabilization of p22(phox) following the binding of bacteria to host cell surface proteins.
 ...
PMID:Degradation of p22phox and inhibition of superoxide generation by Ehrlichia chaffeensis in human monocytes. 1708 35

Some evidence exists that peripheral neutrophils from patients with chronic periodontitis generate higher levels of reactive oxygen species (ROS) after Fcgamma-receptor stimulation than those from healthy controls. We hypothesized that peripheral neutrophils in periodontitis also show both hyper-reactivity to plaque organisms and hyperactivity in terms of baseline, unstimulated generation and release of ROS. Peripheral neutrophils from chronic periodontitis patients and age/sex/smoking-matched healthy controls (18 pairs) were assayed for total ROS generation and extracellular ROS release, with and without stimulation (Fcgamma-receptor and Fusobacterium nucleatum), using luminol and isoluminol chemiluminescence. Assays were performed with and without priming with Escherichia coli lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phox gene expression (p22, p47, p67, gp91) was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Neutrophils from patients produced higher mean levels of ROS in all assays. Total generation and extracellular release of ROS by patients' cells were significantly greater than those from controls after FcgammaR-stimulation, with (P = 0.023) and without (P < or = 0.023) priming with GM-CSF. Differences in unstimulated total ROS generation were not significant. By contrast, patients' cells demonstrated greater baseline, extracellular ROS release than those from controls (P = 0.004). This difference was maintained after priming with LPS (P = 0.028) but not GM-CSF (P = 0.217). Phox gene expression was similar in patient and control cells at baseline and stimulation with F. nucleatum (3 h) consistently reduced gp91(PHOX) transcripts. Our data demonstrate that peripheral neutrophils from periodontitis patients exhibit hyper-reactivity following stimulation (Fcgamma-receptor and F. nucleatum) and hyperactivity in terms of excess ROS release in the absence of exogenous stimulation. This hyperactive/-reactive neutrophil phenotype is not associated with elevated phox gene expression.
 ...
PMID:Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis. 1722 66

Reactive oxygen species (ROS) modulate intracellular signaling but are also responsible for neuronal damage in pathological states. Microglia, the resident CNS macrophages, are prominent sources of ROS through expression of the phagocyte oxidase which catalytic subunit Nox2 generates superoxide ion (O2(.-)). Here we show that microglia also express Nox1 and other components of nonphagocyte NADPH oxidases, including p22(phox), NOXO1, NOXA1, and Rac1/2. The subcellular distribution and functions of Nox1 were determined by blocking Nox activity with diphenylene iodonium or apocynin, and by silencing the Nox1 gene in microglia purified from wild-type (WT) or Nox2-KO mice. [Nox1-p22(phox)] dimers localized in intracellular compartments are recruited to phagosome membranes during microglial phagocytosis of zymosan, and Nox1 produces O2(.-) in zymosan-loaded phagosomes. In microglia activated with lipopolysaccharide (LPS), Nox1 produces O2(.-), which enhances cell expression of inducible nitric oxide synthase and secretion of interleukin-1beta. Comparisons of microglia purified from WT, Nox2-KO, or Nox1-KO mice indicate that both Nox1 and Nox2 are required to optimize microglial production of nitric oxide. By injecting LPS in the striatum of WT and Nox1-KO mice, we show that Nox1 also enhances microglial production of cytotoxic nitrite species and promotes loss of presynaptic proteins in striatal neurons. These results demonstrate the functional expression of Nox1 in resident CNS phagocytes, which can promote production of neurotoxic compounds during neuroinflammation. Our study also shows that Nox1- and Nox2-dependent oxidases play distinct roles in microglial activation and that Nox1 is a possible target for the treatment of neuroinflammatory states.
 ...
PMID:Neurotoxic activation of microglia is promoted by a nox1-dependent NADPH oxidase. 1900 69


1 2 Next >>