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)

The metabolic events occurring during the respiratory burst of macrophages previously primed in vivo with lipopolysaccharide were studied by 31P nuclear magnetic resonance, using the P388D1 cell line as a model of the mature macrophages. Using perchloric acid extracts, the presence of phosphocreatine was shown in the primed cells, indicating that in control P388 D1 macrophages, in which no phosphocreatine was seen, in vivo maturation was incomplete. The cells primed in vivo exhibited greater maturation than the control cells, as well as greater creatine kinase activity. Perfusion of gel-embedded macrophages allowed the monitoring of phosphorylated metabolite peak intensities and of the intracellular pH. After the respiratory burst of the primed macrophages had been triggered by concanavalin A, these intensities did not alter significantly, but the intracellular pH decreased. 31P NMR spectra reflected transient acidification in the primed cells, possibly due to the formation of endocytic vesicles and their fusion with lysosomes.
 ...
PMID:31P NMR study of intracellular pH during the respiratory burst of macrophages. 215 52

Endotoxemia occurs when intestinal ischemia allows bacterial lipopolysaccharide to translocate from colonic flora into the bloodstream, which triggers release of cytokines that can cause hypotension, rigors, fever, shock, and even death. Recently, blood endotoxin levels were shown to be higher in athletes needing medical attention (330 pg.ml-1) than in their competitors with similar performances (81 pg.ml-1). Though there were no data showing that these athletes had elevated core temperatures or severe illness, speculation followed that endotoxin may play a causal role in heat stroke. We examined the relationship between endotoxemia and mild post-exertional illness in 39 cyclists after a 100-mile ride. Thirteen cyclists had at least one of the following: orthostatic hypotension, rigors, nausea, vomiting, diarrhea, or syncope. Only 2/26 case-controls had any of these symptoms. Data were collected on vital signs, hemoglobin, sodium, creatine kinase, creatinine, and uric acid. Endotoxin titer was determined by chromogenic assay; tumor necrosis factor alpha (TNF-alpha) titer was determined by ELISA. One ill cyclist had an endotoxin level of 330 pg.ml-1, one control had an endotoxin level of 150 pg.ml-1, but endotoxin level was < or = 64 pg.ml-1 in all others. Comparison of pre- and post-ride data showed that controls increased creatine kinase activity (154 +/- 34 vs 561 +/- 191 IU.dl, P < 0.05), creatinine concentration (1.5 +/- 0.0 vs 1.6 +/- 0.0 mg.dl-1, P < 0.05), and uric acid concentration (5.4 +/- 0.3 vs 6.3 +/- 0.3 mg.dl-1, P < 0.05). Ill cyclists had lower serum sodium than post-ride controls (138 +/- 2 vs 142 +/- 0.6 mEq.l-1, P < 0.05), but there were no differences between groups in CK, creatinine, or uric acid. These findings suggest that endotoxemia may complicate, but does not cause mild post-exertional illness in cyclists.
 ...
PMID:Exercise-associated collapse in cyclists is unrelated to endotoxemia. 853 21

The liver plays an important role in maintaining homeostasis during endotoxin-triggered systemic inflammatory response. To study the effects of phosphocreatine on hepatic energy metabolism after endotoxin administration, we used transgenic mice whose livers express creatine kinase (CK). CK catalyzes a phosphocreatine/creatine reaction, that is, an adenosine triphosphate (ATP) reservoir system. Because dietary supplementation with creatine leads to an accumulation of creatine and phosphocreatine in transgenic livers, we compared the CK transgenic mice fed with creatine with the normally fed CK transgenic mice. In the creatine-fed mice, hepatic ATP, energy charge ([ATP + 0.5 adenosine diphosphate (ADP)]/[ATP + ADP + adenosine monophosphate (AMP)]), and mitochondrial oxidative phosphorylation activities remained at high levels after injection of 10 mg/kg of lipopolysaccharide (LPS) as compared with those in normally fed mice. Furthermore, there were beneficial effects on the functional reserve for ATP synthesis and work-cost performance, as calculated by free cytoplasmic ADP and the Michaelis constant (Km). Interestingly, a reduction of tissue necrosis factor alpha and interleukin-lalpha (IL-lalpha), and suppression of the decrease in glucose levels after LPS injection were observed in the creatine fed mice. Survival rates at 72 hours after injection of 10 mg/kg of LPS significantly increased in the creatine fed mice compared with the normally fed mice (80% vs. 24%, P < .001). Therefore, we concluded that the presence of phosphocreatine in the liver maintains energy metabolism and attenuates cytokine response, resulting in endotoxin tolerance.
 ...
PMID:Induction of endotoxin tolerance in transgenic mouse liver expressing creatine kinase. 878 40

Myocardial tolerance to ischemia and reperfusion (I/R) injury can be achieved by either acute or delayed cardioprotective mechanisms. Ischemic preconditioning has been demonstrated to be a powerful acute cardioprotective stimulus. We have reported that lipopolysaccharide (LPS) pretreatment induces delayed myocardial adaptation to I/R injury. To optimize myocardial protection, we examined the ability of delayed myocardial adaptation to enhance acute ischemic preconditioning in the isolated working rat heart. Male Sprague-Dawley rats were divided into control, acute [transient ischemia (TI); 5-min global ischemia, 37 degrees C], delayed (LPS; 500 micrograms/kg i.p.), or combined (LPS + TI) cardioprotective groups. Delayed cardioprotection involved LPS injection 72 h before heart isolation. All hearts were subjected to 20-min global ischemia (37 degrees C) and 30-min reperfusion. Coronary effluent collected during reperfusion was assayed for creatine kinase (CK) activity. Both TI and LPS treatment improved postischemic aortic flow recovery (29 +/- 4.5 and 44 +/- 4.0%, respectively; P < 0.05, LPS vs. TI) compared with control hearts (11 +/- 2.2%; P < 0.05, TI or LPS vs. control). When TI was applied to LPS-treated hearts (LPS + TI), aortic flow recovery was further enhanced (57 +/- 3.8%; P < 0.05 vs. TI or LPS alone). CK release during 20 and 30 min of reperfusion was decreased in all treated hearts compared with control hearts (P < 0.05). These results indicate that delayed myocardial adaptation and acute ischemic preconditioning independently activate protective mechanisms against ischemia. Enhanced protection occurs when induced delayed mechanisms are combined with acute cardioprotective stimuli, which optimize postischemic myocardial function and reduce myocellular necrosis.
 ...
PMID:LPS-induced delayed myocardial adaptation enhances acute preconditioning to optimize postischemic cardiac function. 922 50

Purpose. The purpose of this study was to investigate the relationship between hepatic energy status and liver injury during sepsis, using transgenic mice which express creatine kinase in the liver catalyzing the phosphocreatine/creatine system. Methods. Creatine kinase transgenic mice were fed with normal rodent chow or chow containing 10% creatine for 5 days. Lipopolysaccharide (0.2 mg/kg) combined with d-galactosamine (600 mg/kg) was administered intraperitoneally. Results. Eighty percent of the creatine-fed transgenic mice had survived at 48 h post-d-galactosamine and lipopolysaccharide administration, compared with none of the normally fed transgenic mice. Hepatic phosphocreatine and ATP levels in the normally fed transgenic mice were significantly lower than those in the creatine-fed transgenic mice before and after lipopolysaccharide combined with d-galactosamine was administered. Massive hepatic hemorrhagic necrosis with apoptosis was seen in response to d-galactosamine and lipopolysaccharide in normally fed transgenic mice. These results are consistent with a significant increase in serum aminotransferase at 8 h. In contrast, there were faint necrotic changes in the liver with minimal cellular infiltration in creatine-fed transgenic mice. Conclusions. Maintenance of hepatic ATP levels protects from sepsis-induced liver injury and mortality.
 ...
PMID:The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death. 987 18

Previous studies have proposed that endogenous antioxidants play a protective role against cardiac ischemia-reperfusion injury in endotoxin pretreatment. However, the mechanism underlying this effect remains elusive. We therefore evaluated the role of endogenous antioxidants in delayed myocardial protection after different doses of endotoxin administration using cultured rat neonatal cardiomyocytes. Myocytes were treated with normal saline (control) or lipopolysaccharide (Escherichia coli, serotype O111) at doses of 40 and 80 microg/ml (ET40 and ET80). Also, antisense oligodeoxyribonucleotide (1.5 micromol/L) to manganese superoxide dismutase (Mn-SOD) and 3-amino-1,2,4-triazole (25 mg/ml) were added along with a 40 or 80 microg/ml endotoxin pretreatment in the IET40 and IET80 groups. Twenty-four hours later, Cells were subjected to hypoxia (pO2 < 1 kPa, 3 h) and reoxygenation (pO2: 19 kPa, 1 h). Compared with controls, cell viability enhanced significantly (65.3 +/- 5.9, 63.8 +/- 4.6, and 69.7 +/- 5.2% vs 47.2 +/- 4.3%, P < 0.05) and creatine kinase release decreased (7.34 +/- 1.76, 7.11 +/- 1.49, and 6.27 +/- 1.24 U/mg protein vs 11.23 +/- 2.49 U/mg protein, P < 0. 05) in ET40, IET40, and ET80 groups following reoxygenation. No statistically significant difference was found between the control and the IET80 groups. Furthermore, the levels of Mn-SOD (1.12 +/- 0. 31 vs 0.75 +/- 0.15 U/mg. protein, P < 0.05) and catalase activity (1265 +/- 109 vs 996 +/- 85 U/mg. protein, P < 0.05) were higher only in the ET80 group. The results suggest that at a dose of 40 microg/ml, cells were protected by mechanisms other than the augmentation of endogenous antioxidant activity which were more evident at a dose of 80 microg/ml. It seems that different doses of endotoxin pretreatment may induce delayed myocardial protection through various mechanisms.
 ...
PMID:Different role of antioxidants in endotoxin-induced late myocardial protection. 1009 Aug 28

Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosis factor (TNF) release followed by liver injury were investigated. Intraperitoneal (i.p.) treatment with naringin prior to an intravenous (i.v.) challenge of lipopolysaccharide significantly reduced serum TNF levels in a dose-dependent manner and was the most effective when administered 60 min prior to lipopolysaccharide challenge. Treatment with naringin 3 h prior to lipopolysaccharide challenge resulted in complete protection from lipopolysaccharide lethality in D-galactosamine-sensitized mice. Histological estimation revealed that massive cell infiltration followed by severe injury developed in the livers of lipopolysaccharide-treated and D-galactosamine-treated mice unless they had been pretreated with naringin. Appearance of apoptotic cells was also found to decrease by treatment with naringin. Increases in serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase, responsible for lipopolysaccharide-induced liver injury, blocked by naringin administration and the levels were nearly to the normal level. These results indicate that action of naringin is mediated through suppression of lipopolysaccharide-induced TNF production.
 ...
PMID:Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin. 1019 61

Conscious, male Long Evans rats (350-450 g) chronically instrumented for the measurement of regional haemodynamics, were infused with FR 167653, a dual inhibitor of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) synthesis (0.32 mg/kg/h) for 24 h, beginning 1 h before coinfusion of saline, or with saline for 24 h beginning 1 h before coinfusion of lipopolysaccharide (150 microg/kg/h), or with FR 167653 beginning 1 h before coinfusion of lipopolysaccharide. Animals infused with FR 167653 and saline showed progressive hindquarters vasoconstriction over the 24-h period, but this was not different from the change seen in animals (n = 3) infused with saline alone. However, plasma analysis at the end of the coinfusion of FR 167653 and saline showed substantial elevation in levels of creatine kinase, lactate dehydrogenase, and potassium, consistent with some tissue damage (heart, liver, or skeletal muscle, or a combination of these). Animals coinfused with saline and lipopolysaccharide showed biphasic decreases in mean arterial blood pressure accompanied by renal hyperaemic vasodilatation, and decreases followed by increases in mesenteric and hindquarters flows and vascular conductances. At the end of the infusion period, plasma analysis showed signs of renal dysfunction (elevated creatinine) and hepatic dysfunction (elevated alkaline phosphatase, gamma-glutamyl transferase, and alanine aminotransferase). In the presence of FR 167653, the hypotensive effects of lipopolysaccharide were abolished, but regional haemodynamics were unchanged, as were signs of organ dysfunction. One explanation of these observations is that FR 167653 causes a relative improvement in cardiac function during infusion of lipopolysaccharide, and this opposes the hypotensive effects of the latter, in spite of its persistent vasodilator effects.
 ...
PMID:Influence of FR 167653, an inhibitor of TNF-alpha and IL-1, on the cardiovascular responses to chronic infusion of lipopolysaccharide in conscious rats. 1041 69

The aim of the present study was to establish whether gastro-intestinal (GI) complaints observed during and after ultra-endurance exercise are related to gut ischaemia-associated leakage of endotoxins [lipopolysaccharide (LPS)] into the circulation and associated cytokine production. Therefore we collected blood samples from 29 athletes before, immediately after, and 1, 2 and 16 h after a long-distance triathlon for measurement of LPS, tumour necrosis factor-alpha and interleukin-6 (IL-6). As the cytokine response would trigger an acute-phase response, characteristic variables of these responses were also measured, along with creatine kinase (CK) to obtain an indicator of muscle damage. There was a high incidence (93% of all participants) of GI symptoms; 45% reported severe complaints and 7% of the participants abandoned the race because of severe GI distress. Mild endotoxaemia (5-15 pg/ml) was evident in 68% of the athletes immediately after the race, as also indicated by a reduction in IgG anti-LPS levels. In addition, we observed production of IL-6 (27-fold increase immediately after the race), leading to an acute-phase response (20-fold increase in C-reactive protein and 12% decrease in pre-albumin 16 h after the race). The extent of endotoxaemia was not correlated with the GI complaints or the IL-6 response, but did show a correlation with the elevation in C-reactive protein (r(s) 0.389; P=0.037). Creatine kinase levels were increased significantly immediately post-race, and increased further in the follow-up period. Creatine kinase levels did not correlate with those of either IL-6 or C-reactive protein. It is therefore concluded that LPS does enter the circulation after ultra-endurance exercise and may, together with muscle damage, be responsible for the increased cytokine response and hence GI complaints in these athletes.
 ...
PMID:Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. 1060 Jun 58

The subcellular mechanisms responsible for myocardial depression during sepsis remain unclear. Recent data suggest a role for impaired energy generation and utilization, resulting in altered contractile function. Here, we studied the energetic and mechanical properties of skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia. Thirty-six hours after lipopolysaccharide (LPS) injection (in the presence of altered myocardial contractility), mitochondrial respiration, coupling between oxidation and phosphorylation, and creatine kinase function were similar in preparations from endotoxemic (LPS) and control animals. The maximal Ca2+-activated force was similar in LPS and control preparations. However, the Ca2+ concentration corresponding to half-maximal force (pCa50, where pCa = -log10[Ca2+]) was 5.55 +/- 0.01 (n = 11) in LPS fibers versus 5.61 +/- 0.01 (n = 10) in control fibers (p < 0.01). Both protein kinase A (PKA) and alkaline phosphatase treatment led to the disappearance in the difference between control and LPS pCa50 values. Incubation of control fibers with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) did not change the Ca2+ sensitivity after subsequent skinning, whereas isoproterenol decreased pCa50 from 5.62 +/- 0.01 to 5.55 +/- 0.01 (p < 0.01). These data suggest that during sepsis, cardiac mitochondrial and creatine kinase systems remain unaltered, whereas protein phosphorylation decreases myofibrillar Ca2+ sensitivity and may contribute to the depression of cardiac contractility.
 ...
PMID:Phosphorylation-dependent alteration in myofilament ca2+ sensitivity but normal mitochondrial function in septic heart. 1117 7


1 2 3 4 5 Next >>