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)

Oxidation of low density lipoprotein (LDL) leads to more rapid uptake by arterial wall macrophages and foam cell formation. Inhibiting LDL oxidation may impede these processes and offers a new mechanism to retard atherogenesis. The 21-aminosteroids, derived from methylprednisolone, are potent inhibitors of free radical production by stimulated monocytes and also are scavengers of lipid peroxyl radicals. The 21-aminosteroid, U74500A, was added to a mixture of low density lipoprotein cholesterol and human monocytes to which lipopolysaccharide was add to stimulate the monocytes. At a final concentration of 10 microM, U74500A reduced the production of lipid peroxidation from 6.10 +/- 1.11 to 0.84 +/- 0.16 nmol (mean +/- SEM) MDA equivalent/1 x 10(6) monocytes, as measured by a thiobarbituric acid reacting substance (TBARS) assay. Similarly 10 microns U74500A reduced Cu2+ induced LDL oxidation from 12.28 +/- 0.10 (in vehicle) to 0.49 +/- 0.12. These observations suggest that the 21-aminosteroids should be evaluated in animal models as a potential therapy to retard atherogenesis, especially considering their apparent lack of mineralocorticoid and glucocorticoid side-effects.
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PMID:A 21-aminosteroid inhibits oxidation of human low density lipoprotein by human monocytes and copper. 175 90

The protective effect of melatonin against lipopolysaccharide (LPS)-induced oxidative damage was examined in vitro. Lung, liver, and brain malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations were measured as indices of induced membrane peroxidative damage. Homogenates of brain, lung, and liver were incubated with LPS at concentrations of either 1, 10, 50, 200, or 400 micrograms/ml for 1 h and, in another study, LPS at a concentration of 400 micrograms/ml for either 0, 15, 30, or 60 min. Melatonin at increasing concentrations from 0.01-3 mM either alone or together with LPS (400 micrograms/ml) was used. Liver, brain, and lung MDA + 4-HDA levels increased after LPS at concentrations of 10, 50, 200 or 400 micrograms/ml; this effect was concentration-dependent. The highest levels of lipid peroxidation products were observed after tissues were incubated with an LPS concentration of 400 micrograms/ml for 60 min; in liver and lung this effect was totally suppressed by melatonin and partially suppressed in brain in a concentration-dependent manner. In addition, melatonin alone was effective in brain at concentrations of 0.1 to 3 mM, in lung at 2 to 3 mM, and in liver at 0.1 to 3 mM; in all cases, the inhibitory effects of melatonin on lipid peroxidation were always directly correlated with the concentration of melatonin in the medium. The results show that the direct effect of LPS on the lipid peroxidation following endotoxin exposure is markedly reduced by melatonin.
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PMID:Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in vitro. 858 67

Malonaldehyde (MDA), a product of lipid peroxidation, is a presumptive marker for the development of oxidative stress in tissues and plasmas. In this study we report the photodiode array detection of the 2,4-dinitrophenylhydrazine (DNPH) derivatives of MDA using HPLC. Oxidative stress was produced by injecting (i.p.) bacterial lipopolysaccharide (LPS) into rats at a dose of 100 micrograms/kg, or i.v. into rabbits (1 microgram/kg), or added to freshly drawn human blood (200 ng/ml). Blood was collected at several time points up to 5 h, centrifuged, and equal volumes of 20% TCA were used to precipitate proteins from the plasma. The supernatants were derivatized with DNPH, and the aldehyde-DNPHs were extracted with pentane. After evaporation, aliquots of 10 microliters in acetonitrile were injected onto a Beckman Ultrasphere C18 (3 microns) column, chromatographed with an acetonitrile-water-acetic acid gradient mobile phase and scanned using Waters 996 photodiode array detector. Peak identification and homogeneity was determined by comparing the experimental peaks and UV scans with those of authentic standards. A significant increase in the DNPH derivative of malonaldehyde (MDA-DNPH), but not of the other aldehyde-DNPH derivatives of formaldehyde (FDA), acetaldehyde (ADA), acetone and propionaldehyde (PDA) was seen over the first hour after LPS administration in anesthetized rats, while in conscious rabbits this trend lasted up to 3 h. The retention times as well as the UV scans of the derivatized aldehydes matched the authentic standards. Thus, photodiode array detection has proved valuable in establishing this HPLC method for estimating oxidative stress. This technique could accurately measure pmol amounts of MDA-DNPH indicating the usefulness of photodiode array detection method for estimating small changes in the oxidative stress.
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PMID:High-performance liquid chromatographic peak identification of 2,4-dinitrophenylhydrazine derivatives of lipid peroxidation aldehydes by photodiode array detection. 954 33

Inositol hexaphosphate (IP6) has received much attention for its role in interfering with tumor progression and slowing the metastasis of neoplastic cells. However, there is little information regarding the antioxidant properties of IP6 or its ability to enhance the natural disease resistance of the body. The specific objectives of this experiment were to investigate the effects that IP6 might have on the proliferation and viability of RAW 264.7 transformed macrophages and to morphologically and biochemically investigate the role of IP6 as a free radical scavenger. Transformed RAW macrophages were obtained from the American Type Culture Collection (Rockville, MD) and maintained in sterile media (RPMI) supplemented with 10% fetal bovine serum and 1% antibiotics and antimycotics. The cells were plated on to 24 well plates at a density of 1 x 10(5) cells/well. The cells were divided into five groups of four wells per group per phase (24, 48, and 72 hours). Cells in Group I were treated with media alone and served as controls. Cells in Group II were treated with lipopolysaccharide (LPS) only. Cells in groups III, IV, and V were treated with 1000 microliters of IP6 + LPS, 500 microliters of IP6 + LPS, and 100 microliters of IP6 + LPS, respectively. Cell numbers, as well as, morphology, MDA, and protein were determined at the end of 24, 48, and 72 hours. Data obtained from this investigation revealed that the rate of cell proliferation was totally dependent on the dose of IP6. At 24 and 48 hours and upon the exposure of high dose of IP6 the mitotic ability of the cells was higher (p < 0.05) than the rate at the 72 hour phase. Morphological evaluation of cells at all three phases revealed that there were significant changes in the architecture of cells upon the exposure of IP6 compared to the control group. The results of this study suggest that IP6 may have had an excitatory effect on the inflammatory cell secretions and this phenomenon was found to be dose dependent.
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PMID:The effects of inositol hexaphosphate on the inflammatory response in transformed RAW 264.7 macrophages. 1083 3

The effect of adrenal hormones namely dehydroepiandrosterone (DHEA, 10-50 ug/day) and androstenedione (AED, 10-50 ug/day), on RAW 264.7 macrophage survival at 24, 48 and 72 hours after lipopolysaccharide (LPS, 2 micrograms/ml) exposure was investigated in an in vitro environment. RAW cells were obtained from American Type Culture Collection and standard laboratory protocols were followed in cells plating (10(6) cells/well), phase terminating, morphological evaluation, and biochemical marker analysis. From physiologic to supraphysiologic doses of DHEA and AED at 24 hours caused increased levels of cellular proteins and cell number without causing any significant (p < 0.05) change in cellular membrane integrity (Maliondialdehyde, MDA) or viability (morphology). At 48 and 72 hours, cells treated with either AED or DHEA did not sustain the increased cellular proliferation as observed at 24 hours and did not significantly differ (p < 0.05) in cellular protein content. RAW 264.7 cells treated with LPS for 30 minutes prior to AED or DHEA exposure caused slight decrease in cell number and cell protein content. The decrease in both cell number and cell protein content were not attributed to increased cell damage or decreases in cell viability due to the fact that the cellular MDA levels were not statistically higher than the control values (p < 0.05). Morphological Evaluations of cells using Image Pro Software, revealed no significant or adverse changes when compared with cells treated with media alone. Dot blot analysis of pro-inflammatory cytokine (TNF alpha) production after LPS treatment was suppressed by DHEA while AED had a minor influence on the responses. These data imply that LPS mediated activation of RAW 264.7 cells can be inhibited by the addition of pharmacological doses of adrenal hormones such as DHEA.
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PMID:Morphological and biochemical evaluation of RAW 264.7 macrophages after acute and chronic administration of DHEA and AED. 1083 58

This study was undertaken to investigate the antitumor effect of liposomal hexadecylphosphocholine (L-HPC), a synthetic phospholipid encapsulated into multilamellar vesicles (MLV). The effect of these liposomes was tested in an orthotopic nude mouse model using the human mammary carcinomas MDA-MB 435 and 231. The main interest of the investigation was to study whether activated macrophages are substantially involved in the tumor growth inhibition mechanism. The growth of both MDA-MB 435 and 231 tumors in the mammary fat pad was significantly inhibited by a 14-day intraperitoneal therapy with L-HPC. The remaining tumors were shown to be heavily infiltrated with macrophages. In vitro studies of mPEM demonstrated a significant induction of macrophage-mediated tumor cytotoxicity (MMCTX) against the 2 cell lines by L-HPC. The L-HPC-mediated activation mechanism was characterized to be IL-6 and TNFalpha dependent but rather independent of IL-1alpha and nitric oxide (NO). NMA, a specific inhibitor of NO production, did not inhibit L-HPC-induced MMCTX. Furthermore, L-HPC was shown to upregulate the matrixmetalloproteinases MMP-9 and MMP-2 secretion into the supernatant. Considering cytokine release and production of collagenases, the L-HPC-induced macrophage activation cascade is assumed to be comparable with that of classical activators such as lipopolysaccharide (LPS) and interferon (IFN) gamma. As far as NO production is considered, the L-HPC activation mechanism differs from that caused by LPS and IFN gamma.
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PMID:Growth inhibition of human mammary carcinoma by liposomal hexadecylphosphocholine: Participation of activated macrophages in the antitumor mechanism. 1129 Oct 82

The major goal of this study was to examine the ability of several antioxidants namely, vitamin E, beta-carotene and N-acetylcysteine, to protect the brain from oxidative stress induced by lipopolysaccharide (LPS, endotoxin). LPS, a component of the bacterial wall of gram-negative bacteria, has been recognized as one of the most potent bacterial products in the induction of host inflammatory responses and tissue injury and was used in this study to mimic infections. LPS injection resulted in a significant increase in the stress indices, plasma corticosterone and glucose concentration, a significant alteration of the brain oxidative status observed as elevation of the level of malondialdehyde (MDA, index of lipid peroxidation) and reduction of reduced glutathione (GSH), and a disturbance in the brain energy metabolism presented as a reduction in the ATP/ADP ratio and an increase in the mitochondrial/cytosolic hexokinase ratio. However, the activities of brain superoxide dismutase and Na+, K+-ATPase and contents of cholesterol and phospholipids were not altered. Administration of the aforementioned antioxidants prior to LPS injection ameliorated the oxidative stress by reducing levels of MDA, restoring GSH content and normalizing the mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering levels of plasma corticosterone and glucose. In conclusion, this study showed the increased free radical generation during infections and LPS-induced stress. It also suggests that brain oxidative status and energy is disturbed.
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PMID:Protective effect of vitamin E, beta-carotene and N-acetylcysteine from the brain oxidative stress induced in rats by lipopolysaccharide. 1133 Dec 2

To study the alterations of heme oxygenase-1 mRNA in neonatal rat cardiomyocytes (NRCMs) induced by lipopolysaccharide (LPS) and the role of heme oxygenase-1 (HO-1) in the LPS induced disorders of myocardium function, 10 (L, 6 h), 30 (M, 6 h), 50 micrograms/ml (H, 6 h) LPS and 10 micrograms/ml LPS + 10 mumol/ml Zn-protoporphyrin-IX (ZnPPIX; L + I, 6 h) and 10 mumol/ml ZnPPIX alone (I, 6 h) were added to the medium for a 6-hour culture of NRCMs, and 10 micrograms/ml LPS for 9 h (L, 9 h) and 18 h (L, 18 h) cultures. LDH release and MDA contents of the cells were measured. When NRCMs were collected, Trypan blue stain method was used to examine the mortality (the rate of Trypan blue uptake) of NRCMs. HO-1 mRNA expression was examined by Northern blot. The results showed that HO-1 mRNA expression of NRCMs increased gradually along with the increase of LPS concentration below the level of 30 micrograms/ml. When the final concentrations of LPS were 10 and 30 micrograms/ml, the HO-1 mRNA expression of NRCMs increased by 81.2% and 126.3% respectively compared with control. When the final concentration of LPS was 50 micrograms/ml, the HO-1 mRNA expression decreased to the level of 10 micrograms/ml group. When the final concentration was 10 micrograms/ml, the HO-1 mRNA expression increased gradually along with the culture time. After a 9- or 18-hour culture, the HO-1 mRNA expression of NRCMs increased by 93.6% and 105.8% respectively compared with control. Only when NRCMs had been cultured with 30, 50 micrograms/ml LPS and 10 micrograms/ml LPS + 10 mumol/ml ZnPPIX for 6 h and 10 micrograms/ml LPS for 18 h, the rate of Trypan blue stain uptake, MDA contents and LDH release significantly increased. With 10 micrograms/ml LPS alone and 10 mumol/ml ZnPPIX alone for 6 h, the above parameters were not significantly increased (P > 0.05). The results demonstrate that LPS induces HO-1 mRNA expression of NRCMs dose- and time-dependently to some extent. The inducible HO can protect NRCMs from injury and thus play an important role in pathogenesis of myocardium under LPS.
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PMID:[Expression of heme oxygenase-1 in neonatal rat cardiocytes induced by lipopolysaccharide]. 1135 95

In murine macrophages, the anti-tumor agent, paclitaxel, induces expression of a wide variety of inflammatory and anti-inflammatory genes, and causes cytokine secretion via signaling pathways that overlap with those engaged by lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Using semi-quantitative RT-PCR for detection of gene expression, coupled with ELISA for the detection of secreted gene products, we analyzed the responsiveness of an extensive panel of cytokine and non-cytokine genes to induction by paclitaxel and LPS in the murine DA-3 breast cancer line. A subset of the genes examined (e.g., G-CSF, MIP-2, iNOS, and IL-1 beta, and GM-CSF) was upregulated >3-20-fold by both LPS and paclitaxel in the DA-3 cell line, while IP-10 mRNA was induced by paclitaxel, but not by LPS. In the human MDA-MB-231 breast cancer cell line, LPS also increased mRNA levels for both GM-CSF and IP-10 significantly, while, paclitaxel increased IP-10 mRNA levels with delayed kinetics and failed to induce GM-CSF mRNA. Co-cultures of murine breast cancer cells and macrophages, stimulated with IFN-gamma plus either paclitaxel or LPS, resulted in augmented release of nitric oxide. As both GM-CSF and IP-10 have been implicated in tumor rejection in vivo through either indirect actions on the host immune system or by inhibiting tumor angiogenesis, our data strengthen the hypothesis that tumor cell-derived inflammatory mediators may, in part, underlie the anti-tumor efficacy of paclitaxel in breast cancer.
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PMID:Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. 1155 85

Cyclooxygenase (COX)-2, the inducible prostaglandin synthase, is overexpressed in cancer and chronic inflammatory diseases. Post-transcriptional regulation of COX-2 mRNA is important in controlling the expression of the COX-2 gene. Here, we report that leptomycin B (LMB), a specific inhibitor of the nuclear export factor CRM1 potently inhibits the stabilization of COX-2 mRNA in MDA-MB-231 human mammary cancer cells. However, COX-2 promoter-driven reporter gene expression is not inhibited by LMB, suggesting that LMB acts at the post-transcriptional level. Subcellular fractionation experiments indicate that LMB inhibited the time-dependent export of COX-2 mRNA into the membrane-bound polysomal compartment at the endoplasmic reticulum. LMB suppressed COX-2 expression by interleukin-1beta in HT-29 human colon cancer cells and in human umbilical vein endothelial cells but had no effect on COX-2 expression induced by Escherichia coli lipopolysaccharide in monocytic THP-1 cells. These data suggest that the nuclear export of COX-2 mRNA may be rate-liming in a cell-specific manner. LMB may be useful to control COX-2 expression in various human diseases in which COX-2 plays a pathogenetic role.
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PMID:Leptomycin B, an inhibitor of the nuclear export receptor CRM1, inhibits COX-2 expression. 1246 43


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