Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon induction occurred unexpectedly during an in vivo study using a mouse monoclonal antibody. The interferon was typed alpha/beta and the titer reached a maximum at 24 hours in contrast with other inducers. Similar results were obtained with a virus pool derived from the antibody and with a LDV reference strain. MAP-testing of the monoclonal antibody revealed contamination with lactate dehydrogenase virus (LDV). The production of IFN seems to be controlled genetically. This experimental error demonstrates the importance of an appropriate quality control of biological materials.
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PMID:Contamination of a monoclonal antibody with LDH-virus causes interferon induction. 245 6

The effects of sea snake venom (SSV) on renal function were studied in two groups of anesthetized experimental dogs pretreated with intravenous infusion of 4.2 gm% NaHCO3 solution. Animals were envenomated by intramuscular injection of SSV at a dosage of 0.34 mg/kg. Systemic hemodynamics showed no significant changes except for a tendency of decrease in cardiac output (CO). The glomerular filtration rate (GFR), the rate of urine flow (V) and effective renal plasma flow (ERPF), and effective renal blood flow (ERBF) significantly decreased, while filtration fraction (FF) significantly increased at 180 min after envenomation. Envenomated animals showed a reduction in renal fraction (RF), while renal vascular resistance (RVR) increased stepwise throughout the experimental periods. Animals pretreated with sodium bicarbonate showed no significant changes of CO, TPR MAP, HR, and packed cell volume (PCV) while receiving sea snake venom. Animals pretreated with sodium bicarbonate showed no changes in GFR, ERPF, ERBF, RF, and RVR after envenomation. The rate of urine flow markedly increased in envenomated animals which received pretreatment with bicarbonate. After envenomation alone, there were no differences in the plasma concentration of sodium (PNa) and chloride (PCl) as compared to the control value, whereas the plasma concentration of potassium (PK) increased at 180 min after envenomation. Animals pre-treated with bicarbonate showed a stepwise increase in both UNaV, FE(NA), U(Cl)V, and FE(Cl) accompanying SSV injection. Neither PNa nor PCl were affected, while PK significantly decreased in animals given SSV with bicarbonate loading. UKV and FEK increased stepwise in envenomated animals treated with bicarbonate throughout the period of study. All groups of animals given SSV, with or without NaHCO3 infusion, showed a marked elevation of the concentration of urinary myoglobin (U(Mb)), plasma lactate dehydrogenase (LDH), and plasma creatine phosphokinase (CPK) throughout experimental periods. The urinary myoglobin excretion markedly increased in animals after SSV injection accompanied by NaHCO3 infusion. It can be concluded that large amounts of myoglobin present in the renal tubules in envenomated animals can precipitate, particularly under acidic conditions, resulting in increased intratubular pressure and subsequently decreased renal hemodynamics including GFR and ERBF. An infusion of NaHCO3 to render urine more alkaline could have a protective role against depression of renal function following sea snake venom administration.
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PMID:Renal function following sea snake venom (Lapemis hardwicki) administration in dogs treated with sodium bicarbonate solution. 1200 11

While the molecular basis underlying the non-classical actions of acetylcholinesterase (AChE) is presently unknown, a candidate peptide sequence located at the C-terminus of AChE (AChE-peptide) has recently been identified. This study explored the bioactivity of synthetic AChE-peptide using in vitro organotypic cultures of rat hippocampus. Neurotrophic effects, detected as increased neurite outgrowth from MAP-immunopositive neurones, were apparent using 1 h exposure to 1-10 nM AChE-peptide. As exposure time increased, cell death occurred as indicated by TdT-mediated dUTP biotin nick-end labelling (TUNEL). This process was accelerated at higher AChE-peptide concentrations, with lactate dehydrogenase (LDH) efflux observed following prolonged exposure to 1-10 microM AChE-peptide. Apoptotic cells were detected by Hoechst 33342 staining following 24 h application of 10 nM AChE-peptide. However, propidium iodide reactivity revealed a simultaneous loss of membrane integrity indicative of necrosis, suggesting that AChE-peptide induces cell death via a continuum of apoptotic and necrotic processes. Prolonged exposure to AChE-peptide also resulted in a concentration-dependent reduction in neurite outgrowth from MAP2-positive neurons, although immunohistochemical studies provided some evidence of differential responsiveness in GABAergic, cholinergic and somatostatin neurones. In addition, bioactivity was sequence specific since a scrambled AChE-peptide analogue, as well as the corresponding BuChE-peptide, was ineffective. In conclusion, the bioactivity associated with the AChE-peptide sequence may account for the non-cholinergic actions of AChE, whilst its neurotrophic-apoptotic-necrotic spectrum of action may be involved in the aetiology of neurodegenerative disorders such as Alzheimer's disease.
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PMID:Bioactivity of a peptide derived from acetylcholinesterase in hippocampal organotypic cultures. 1468 7

This study was designed to determine the anti-proliferative, apoptotic properties of a novel polysaccharide from the loach, Misgurnus anguillicaudatus (MAP), using a human promyelocytic leukemia line (HL-60) as a model system. HL-60 cells were cultured in the presence of MAP at various concentrations (50-800 mg/l) for 5 days and the percentage of cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results showed that MAP inhibited the cells viability in time and concentration-dependent characteristics. We found that anti-proliferative effect of MAP was associated with apoptosis on HL-60 cells by determinations of morphological changes and oligonucleosomal DNA fragments. In addition, the content of nitric oxide (NO) and activity of lactate dehydrogenase (LDH) release increased when the cells incubated with MAP at various concentrations and times. These investigations suggest that the polysaccharide from loach has the function of anti-proliferation and induction of apoptosis in tumor cells in vitro.
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PMID:Apoptosis induction on HL-60 cells of a novel polysaccharide from the mucus of the loach, Misgurnus anguillicaudatus. 1593 80

Spore-extracted toxins of the indoor mold Stachybotrys chartarum (SC) caused cytotoxicity (release of lactate dehydrogenase), inhibition of cell proliferation, and cell death in murine alveolar macrophage cell line MH-S in a dose- and time-dependent manner. Apoptotic cell death, confirmed based on morphological changes, DNA ladder formation, and caspase 3/7 activation, was detectable as early as at 3 h during treatment with a toxin concentration of 1 spore equivalent/macrophage and was preceded by DNA damage beginning at 15 min, as evidenced by DNA comet formation in single cell gel electrophoresis assay. The apoptotic dose of SC toxins did not induce detectable nitric oxide and pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) but showed exacerbated cytotoxicity in presence of a non-apoptotic dose of the known pro-inflammatory agent LPS (10 ng/ml). Intracellular reduced glutathione (GSH) level showed a significant decrease beginning at 9 h of the toxin treatment whereas oxidized glutathione (GSSG) showed a corresponding significant increase, indicating a delayed onset of oxidative stress in the apoptosis process. The toxin-treated macrophages accumulated p53, an indicator of DNA damage response, and showed activation of the stress-inducible MAP kinases, JNK, and p38, in a time-dependent manner. Chemical blocking of either p38 or p53 inhibited in part the SC toxin-induced apoptosis whereas blocking of JNK did not show any such effect. This study constitutes the first report on induction of DNA damage and associated p53 activation by SC toxins, and demonstrates the involvement of p38- and p53-mediated signaling events in SC toxin-induced apoptosis of alveolar macrophages.
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PMID:DNA damage, redox changes, and associated stress-inducible signaling events underlying the apoptosis and cytotoxicity in murine alveolar macrophage cell line MH-S by methanol-extracted Stachybotrys chartarum toxins. 1647 59

This study was designed to assess the cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion (IR) injury and to explore the mechanism of action of the compound. Sprague Dawley rats were divided into 8 groups (n=10-12): a sham-operated control and 7 ischemia-reperfusion groups (IR control, 3 isosteviol pre-treated (0.5, 1.0 and 2.0 mg kg(-1)), ligustrazine pre-treated, 5-hydroxydecanoate (5-HD) pre-treated and 5-HD+ isosteviol pre-treated groups). IR was produced by occluding the left coronary artery for 30 min followed by re-opening the artery for 90 min. The compounds under investigation were administered intravenously 10 min prior to occluding the artery. Hemodynamic parameters (+/-dp/dt(max), LVSP, LVDevP, MAP), heart rate, ventricular tachycardia (VT) and ventricular fibrillation (VF) were determined during the IR period. The myocardial infarct size, activities of serum lactate dehydrogenase and creatine kinase were determined at the end of the experiment. In the isosteviol pre-treated groups, the hemodynamic parameters were improved and the myocardial infarct size, the activities of serum enzymes, and the incidences of VT and VF were all decreased when compared to the control group. These effects of isosteviol were similar to that of a traditional cardioprotective agent, ligustrazine. The 5-HD+ isosteviol group displayed parameters that were between those in the equivalent isosteviol pre-treated group and the IR control group. In conclusion, damage due to a standard rat heart IR injury was reduced by pretreatment with intravenous isosteviol, and this effect was partly attenuated by a mitochondrial ATP-sensitive potassium channel blocker, 5-HD.
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PMID:The cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion injury. 1705 1

Hemorrhage and resuscitation (H/R) leads to phosphorylation of mitogen-activated stress kinases, an event that is associated with organ damage. Recently, a specific, cell-penetrating, protease-resistant inhibitory peptide of the mitogen-activated protein kinase c-JUN N-terminal kinase (JNK) was developed (D-JNKI-1). Here, using this peptide, we tested if inhibition of JNK protects against organ damage after H/R. Male Sprague-Dawley rats were treated with D-JNKI-1 (11 mg/kg, i.p.) or vehicle. Thirty minutes later, rats were hemorrhaged for 1 h to a MAP of 30 to 35 mmHg and then resuscitated with 60% of the shed blood and twice the shed blood volume as Ringer lactate. Tissues were harvested 2 h later. ANOVA with Tukey post hoc analysis or Kruskal-Wallis ANOVA on ranks, P < 0.05, was considered significant. c-JUN N-terminal kinase inhibition decreased serum alanine aminotransferase activity as a marker of liver injury by 70%, serum creatine kinase activity by 67%, and serum lactate dehydrogenase activity by 60% as compared with vehicle treatment. The histological tissue damage observed was blunted after D-JNKI-1 pretreatment both for necrotic and apoptotic cell death. Hepatic leukocyte infiltration and serum IL-6 levels were largely diminished after D-JNKI-1 pretreatment. The extent of oxidative stress as evaluated by immunohistochemical detection of 4-hydroxynonenal was largely abrogated after JNK inhibition. After JNK inhibition, activation of cJUN after H/R was also reduced. Hemorrhage and resuscitation induces a systemic inflammatory response and leads to end-organ damage. These changes are mediated, at least in part, by JNK. Therefore, JNK inhibition deserves further evaluation as a potential treatment option in patients after resuscitated blood loss.
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PMID:A peptide inhibitor of C-jun N-terminal kinase modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation. 1862 89

Amphotericin B (AMB) is one of the most effective antifungal agents; however, its use is often limited by the occurrence of adverse events, especially nephrotoxicity. The present study was designed to determine the possible mechanisms underlying the nephrotoxic action of AMB. The exposure of a porcine proximal renal tubular cell line (LLC-PK1 cells) to AMB caused cell injury, as assessed by mitochondrial enzyme activity, the leakage of lactate dehydrogenase, and tissue ATP depletion. Propidium iodide uptake was enhanced, while terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was not affected by AMB, suggesting a lack of involvement of apoptosis in AMB-induced cell injury. The cell injury was inhibited by the depletion of membrane cholesterol with methyl-beta-cyclodextrin, which lowered the extracellular Na(+) concentration or the chelation of intracellular Ca(2+). The rise in the intracellular Ca(2+) concentration may be mediated through the activation of the ryanodine receptor (RyR) on the endoplasmic reticulum and the mitochondrial Na(+)-Ca(2+) exchanger, since cell injury was attenuated by dantrolene (an RyR antagonist) and CGP37157 (an Na(+)-Ca(2+) exchanger inhibitor). Moreover, AMB-induced cell injury was reversed by PD169316 (a p38 mitogen-activated protein [MAP] kinase inhibitor), c-Jun N-terminal kinase inhibitor II, and PD98059 (a MEK1/2 inhibitor). The phosphorylations of these MAP kinases were enhanced by AMB in a calcium-independent manner, suggesting the involvement of MAP kinases in AMB-induced cell injury. These findings suggest that Na(+) entry through membrane pores formed by the association of AMB with membrane cholesterol leads to the activation of MAP kinases and the elevation of the intracellular Ca(2+) concentration, leading to renal tubular cell injury.
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PMID:Amphotericin B-induced renal tubular cell injury is mediated by Na+ Influx through ion-permeable pores and subsequent activation of mitogen-activated protein kinases and elevation of intracellular Ca2+ concentration. 1913 82

Inhibition of c-Jun N-terminal kinase (JNK) by a cell-penetrating, protease-resistant JNK peptide (D-JNKI-1) before hemorrhage and resuscitation (H/R) ameliorated the H/R-induced hepatic injury and blunted the proinflammatory changes. Here we tested the hypothesis if JNK inhibition at a later time point-after hemorrhagic shock but before the onset of resuscitation-in a rat model of H/R also confers protection. Twenty-four male Sprague-Dawley rats (250 - 350 g) were randomly divided into 4 groups: 2 groups of shock animals were hemorrhaged to a MAP of 32 to 37 mmHg for 60 min and randomly received either D-JNKI-1 (11 mg/kg i.p.) or sterile saline as vehicle immediately before the onset of resuscitation. Two groups of sham-operated animals underwent surgical procedures without H/R and were either D-JNKI-1 or vehicle treated. Rats were killed 2 h later. Serum activity of alanine aminotransferase and serum lactate dehydrogenase after H/R increased 3.5-fold in vehicle-treated rats as compared with D-JNKI-1-treated rats. Histopathological analysis revealed that hepatic necrosis and apoptosis (hematoxylin-eosin, TUNEL, and M30, respectively) were significantly inhibited in D-JNKI-1-treated rats after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as markers of inflammation (hepatic and serum IL-6 levels and hepatic infiltration with polymorphonuclear leukocytes) were also reduced in D-JNKI-1-treated rats. LPS-stimulated TNF-alpha release from whole blood from hemorrhaged and resuscitated animals was higher in vehicle-treated rats as compared with D-JNKI-1-treated rats. c-Jun N-terminal kinase inhibition after hemorrhage before resuscitation resulted in a reduced activation of c-Jun. Taken together, these results indicate that D-JNKI-1 application after hemorrhagic shock before resuscitation blunts hepatic damage and proinflammatory changes during resuscitation. Hence, JNK inhibition is even protective when initiated after blood loss before resuscitation. These experimental results indicate that the JNK pathway may be a possible treatment option for the harmful consequences of H/R.
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PMID:Inhibition of c-Jun N-terminal kinase after hemorrhage but before resuscitation mitigates hepatic damage and inflammatory response in male rats. 1929 84

The present study evaluated cardioprotective effect of lyophilized hydroalcoholic extract of Moringa oleifera in the isoproterenol (ISP)-induced model of myocardial infarction. Wistar albino male rats were divided into three groups and orally fed saline once daily alone (sham) or with ISP (ISP control) or ISP with M. oleifera (200 mg/kg), respectively, for 1 month. On days 29 and 30 of administration, rats of the ISP control and M. oleifera-ISP groups were administered ISP (85 mg/kg, s.c.) at an interval of 24 hours. On day 31, hemodynamic parameters (mean arterial pressure [MAP], heart rate [HR], left ventricular end-diastolic pressure [LVEDP], and left ventricular peak positive [(+) LV dP/dt] and negative [(-) LV dP/dt] pressures were recorded. At the end of the experiment, the animals were sacrificed, and hearts were excised and processed for biochemical, histopathological, and ultrastructural studies. Chronic treatment with M. oleifera demonstrated mitigating effects on ISP-induced hemodynamic [HR, (+) LV dP/dt, (-) LV dP/dt, and LVEDP] perturbations. Chronic M. oleifera treatment resulted in significant favorable modulation of the biochemical enzymes (superoxide dismutase, catalase, glutathione peroxidase, lactate dehydrogenase, and creatine kinase-MB) but failed to demonstrate any significant effect on reduced glutathione compared to the ISP control group. Moringa treatment significantly prevented the rise in lipid peroxidation in myocardial tissue. Furthermore, M. oleifera also prevented the deleterious histopathological and ultrastructural perturbations caused by ISP. Based on the results of the present study, it can be concluded that M. oleifera extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, antiperoxidative, and myocardial preservative properties.
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PMID:Moringa oleifera leaf extract prevents isoproterenol-induced myocardial damage in rats: evidence for an antioxidant, antiperoxidative, and cardioprotective intervention. 1929 95


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