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

36 dogs were divided into 3 groups: group A were administered with non-oxygenated crystalloid solution as a control; group B, with oxygenated crystalloid solution; group C, with oxygenated no 3 perfluorocarbon emulsion (PFC-O2) as volume expander. Result of measurements of serum CPK, LDH, lactic acid, gas analysis, MAP, and dynamic heart function (including pulmonary water index, LVET, LVEF, SV, CO and HR) and ultrastructural observation on lung tissue and skeletal muscles showed that oxygenated crystalloid solution can more quickly revert the hemodynamic changes after hemorrhagic shock, improves oxygen-utilizing ability of the tissue, and therefore possesses a good protective effect of the organ cells.
 ...
PMID:[Effects of oxygenated volume expander on hemorrhagic shock]. 236 10

Because gut-derived factors carried in mesenteric lymph are implicated in multiple organ dysfunction syndrome and have been shown to injure endothelial cells, we investigated several cellular pathways by which this process could occur. To accomplish this, mesenteric lymph (5%, v/v) collected at 1 to 3 h postshock from male rats undergoing trauma (5-cm laparotomy) and hemorrhagic shock (90 min of mean arterial pressure [MAP] of 30 mmHg; T/HS) was tested for endothelial cell cytotoxicity on human umbilical vein endothelial cells (HUVECs). Over 30 pharmacologic agents that had been reported to inhibit endothelial cell death were tested for their ability to prevent T/HS lymph-induced HUVEC cell death. These included agents documented to protect against oxidant-mediated, calcium-mediated, and arachidonic acid pathway-mediated endothelial cell injury and death. These pharmacologic inhibitors were preincubated with HUVECs for 1 h or were added to the HUVECs simultaneously with lymph, and were then incubated for 18 h. Controls were lymph alone, inhibitor alone, or medium alone. Mitochondrial tetrazolium (MTT) and LDH release assays were used to determine cell viability. The inhibitors that significantly protected HUVECs from the cytotoxicity of T/HS lymph (P < 0.001) included the antioxidant combination of vitamins C and E and the antioxidant-lipooxygenase inhibitor nordihydroguaretic acid (NDGA). These agents were equally effective when added simultaneously with lymph or preincubated with the HUVECs, suggesting an extracellular or membrane-bound process. In summary, the inhibitors that provided protection from toxic lymph appear to work at the membrane and are involved in limiting membrane peroxidation. Based on this study, it appears that an oxidant pathway is involved in T/HS lymph-induced endothelial cell injury and death.
 ...
PMID:The role of oxidant-mediated pathways in the cytotoxicity of endothelial cells exposed to mesenteric lymph from rats subjected to trauma-hemorrhagic shock. 1292

Diabetes activates all three groups of MAP kinases in sensory ganglia. Inhibition of this activation for the ERK and p38 groups prevents nerve damage, and agents that improve neuronal function in diabetic rats-antioxidants and aldose reductase inhibitors-also inhibit activation of ERK and p38 in dorsal root ganglia (DRG). However, these same treatments consistently increase activation of JNK. Thus, in DRG from rats with streptozotocin (STZ)-induced diabetes of 12-week duration, the p54/56 isoforms of JNK were activated by 2.75 compared to controls (P <.05). In DRG from diabetic rats treated with a gamma-linolenic acid and alpha-lipoic acid diester (GLA/LA), the activity of the p54/56 isoform was 3.75 that of controls and the p46 isoform was also increased to 1.75 that of controls (both P <.05 compared to both controls and untreated diabetics). We therefore tested the hypothesis that JNK activation is protective. Exposure of rats to diabetes increased activation of JNK in DRG, but treatment with GLA/LA increased this effect (P <.05). Specific inhibition of JNK in primary cultures of DRG neurons using a peptide inhibitor of JNK (JNKi1, 159-600-R100, 7.5 micro M, Alexis Biochemicals) increased the release of LDH and reduced MTT staining; both findings indicate an increase in neuronal damage. Taken together these findings indicate that multiple isoforms of JNK were activated in sensory neurons of diabetic rats, probably by a combination of raised glucose and oxidative stress, and that this activation of JNK serves to protect the neurons from damage.
 ...
PMID:Activation of JNK in sensory neurons protects against sensory neuron cell death in diabetes and on exposure to glucose/oxidative stress in vitro. 1503 1

The efficacy of Withania somnifera (Ws) to limit myocardial injury after ischemia and reperfusion was explored and compared to that of Vit E, a reference standard known to reduce mortality and infarct size due to myocardial infarction. Wistar rats (150-200 g) were divided into six groups and received orally saline (sham, control group), Ws-50/kg (Ws control and treated group) and Vit E-100 mg/kg (Vit E control and treated group) respectively for 1 month. On the 31st day, rats of the control, Vit E and Ws treated groups were anesthetized and subjected to 45 min occlusion of the LAD coronary artery followed by 60 min reperfusion. Hemodynamic parameters: systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), left ventricular peak (+)LVdP/dt and (-)LVdP/dt were monitored. Hearts were removed and processed for histopathological and biochemical studies: Myocardial enzyme viz, creatin phosphokinase (CPK), and antioxidant parameters: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) were estimated. Postischemic reperfusion produced significant cardiac necrosis, depression of left ventricular functions (MAP, LVEDP, (+) and (-)LVdP/dt) and a significant fall in GSH (p < 0.01), SOD, CAT (p < 0.05), LDH and CPK (p < 0.01) as well as an increase in MDA level (p < 0.05) in the control group rats as compared to sham group. The changes in levels of protein and GPx was however, not significant. Ws and Vit E favorably modulated most of the hemodynamic, biochemical and histopathological parameters though no significant restoration in GSH, MAP (with Vit E) were observed. Ws on chronic administration markedly augmented antioxidants (GSH, GSHPx, SOD, CAT) while Vit E did not stimulate the synthesis of endogenous antioxidants compared to sham. Results indicate that Ws significantly reduced myocardial injury and emphasize the beneficial action of Ws as a cardioprotective agent.
 ...
PMID:Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. 1522 84

Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca(2+), changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs).
 ...
PMID:Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro. 1723 15

MAP kinase is associated with delta-opioid receptor (DOR) signaling and plays a role in cell survival/death. Since anisomycin may alter MAP kinase activity and affect neuronal survival, we investigated whether anisomycin alters neuronal response to hypoxic stress and DOR inhibition. The experiments were performed in cultured cortical neurons. MAP kinase activities were determined by immunoblotting and neuronal viability was assessed by LDH leakage and live/dead morphological study. DOR inhibition with naltrindole (10 microM) led to significant injury in normoxic neurons after 24 h of treatment and exacerbated hypoxia-induced injury. Along with the injury, either by hypoxia or naltrindole, phosphorylated p38 increased in a major way, while phosphorylated ERK and JNK had no significant change or slightly decreased. Anisomycin (50 ng/ml) prevented the increase in phosphorylated p38 immunoreactivity induced by naltrindole and reduced the neuronal injury. The results suggest that (1) MAP kinases are differentially involved in neuronal response to hypoxia and DOR inhibition in cortical neurons with phosphorylated p38 immunoreactivity being upregulated and (2) anisomycin attenuates the increase in phosphorylated p38 immunoreactivity and reduces neuronal injury induced by hypoxia and DOR inhibition.
 ...
PMID:Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK. 1739 55

Homocysteine (HCY) is toxic on blood vessels, but a potential direct toxicity of HCY on the heart is unknown. We addressed this issue by exposing H9C2 cardiomyocytes to HCY (0.1-5 mM) for up to 6h. At these concentrations, HCY reduced cell viability, induced necrosis and apoptosis and triggered the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP). This was associated with the intracellular generation of the potent oxidant peroxynitrite. Removing peroxynitrite by the decomposition catalyst FeTPPS considerably reduced LDH release, DNA fragmentation, cleavage of caspase-3 and PARP, and restored normal cell morphology. In additional experiments performed in primary rat ventricular cardiomyocytes, HCY (1 mM, 6h) activated the phosphorylation of the MAP kinases ERK and JNK, two essential stress signaling kinases regulating myocardial apoptosis, hypertrophy and remodeling. These results provide the first demonstration that HCY kills cardiomyocytes through the generation of peroxynitrite and can activate key signaling cascades in the myocardium.
 ...
PMID:Homocysteine induces cell death in H9C2 cardiomyocytes through the generation of peroxynitrite. 1754 63

Cytoresistance is the term used to describe the response of the proximal tubule cells to various stress inducers via cholesterol accumulation. However, the role of extensive exercise as a renal insult has not been examined. In this study, the effect of heavy muscle activity on proximal tubule cytoresistance was investigated. Results obtained from rats subjected to running a treadmill for five days were compared to those of controls. Extensive muscle activity-induced soleus citrate synthase and blood lactate elevation were associated with normal MAP, RBF, and GFR. Blood electrolytes and cholesterol levels remained unchanged, whereas the total and free cholesterol accumulations in the proximal tubule cells of the exercised group were higher than controls. Cholesterol-loaded tubules were more resistant (as proved by LDH release) to an ATP-depleted/calcium overloaded second stress. These data clearly demonstrate that heavy muscle activity induces cholesterol accumulation in the proximal tubules of kidney, without influencing ATP generation.
 ...
PMID:The effect of heavy muscle activity on renal cytoresistance in rats. 1981 35

This study aims to explore the changes in calcium regulation in the sarcoplasmic reticulum (SR) during doxorubicin (DOX) treatment. Sprague-Dawley rats were treated with intravenous DOX (1.5 mg/kg) twice weekly for 12 treatments. The hemodynamic changes, myocardial oxidative stress, levels of cardiac toxicity markers, and calcium handling of the myocardial SR were observed. When the accumulation of DOX reached 12 mg/kg, (1) heart weight, left ventricular mass, and lung congestion increased significantly, and ascites appeared; (2) SBP, DBP, MAP, +dP/dt, -dP/dt, and LVSP decreased significantly, and LVEDP increased (p < 0.01); (3) the iNOS activity and MDA and NO concentrations significantly increased, while the SOD decreased (p < 0.05 or 0.01); (4) the serum level of the AST, LDH CPK, cTnI, and BNP increased significantly (p < 0.01); (5) during DOX treatment, the rat SR Ca(2+) absorption function and Ca(2+)-stimulated ATPase activity declined dramatically, as did the SERCA2 and phospholamban levels (p < 0.01). As expected, all these changes became evident with DOX accumulation in vivo (p < 0.05 or 0.01). In conclusion, DOX induces SR calcium regulation dysfunction via the decrease of SERCA2 and phospholamban expressions in rats.
 ...
PMID:Doxorubicin induces sarcoplasmic reticulum calcium regulation dysfunction via the decrease of SERCA2 and phospholamban expressions in rats. 2502 95

Environmental pollutants are known to have adverse effects on human health. However, the link between chemical exposure and osteoarthritis remains little investigated. This study sought to assess in vitro the effect of several non-dioxin-like polychlorinated biphenyls (NDL-PCBs) on chondrocytes viability and apoptosis induction. Murine chondrogenic ATDC-5 cell line and human T/C-28a2 immortalized chondrocytes were exposed to NDL-PCBs 101, 153 and 180. Cell viability was examined using MTT assay. Necrosis was evaluated by LDH assay. Expression of apoptotic related proteins, such as caspase-3, Bcl-2 and Bax was assessed by Western blot analysis. Finally, oxidative stress was evaluated by malondialdehyde (MDA) assay and the Oxidative Stress Index. In vitro exposure to NDL-PCBs caused strong reduction of cell viability in a concentration-dependent manner. Data from LDH assay showed cellular necrosis induction. Caspase-3 activation, as well as, altered Bcl2/Bax ratio and p38 MAP-kinase phosphorylation also suggested apoptosis induction. Finally, MDA levels and Oxidative Stress Index revealed that PCBs drive chondrocyte death via increase of oxidative stress. The viability of murine and human chondrocytes was reduced in presence of PCBs. The activity of PCBs on cell viability is likely to be mediated by complex alterations involving regulation mechanisms of apoptosis, necrosis and oxidative stress.
...
PMID:Non-dioxin-like polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) induce chondrocyte cell death through multiple pathways. 2565 34


1 2 Next >>