Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitogen-activated protein kinases (MAPKs), a family of signal transduction mediators important in a host of cellular activities, include the extracellular signal-regulated kinases Erk1 and Erk2. We determined whether 5-HT(1A) receptors activate Erk1/2 in rat brain in vivo, as they do in recombinant cell lines. In contrast to the effect in cells, the 5-HT(1A) receptor agonist 8-hydroxy-N,N-diproylaminotetralin (8-OH-DPAT) dose- and time-dependently decreased basal levels of phosphorylated Erk1/2 (phospho-Erk1/2) in rat hippocampus (ED(50) approximately 0.1 mg/kg, maximum approximately 90%) without altering total Erk1/2. The effects were kinase-specific, as 8-OH-DPAT did not modify phosphorylated or total levels of the MAPKs c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 MAPK. Moreover, 8-OH-DPAT did not modify phospho-Erk1/2 in striatum or frontal cortex. The effect of 8-OH-DPAT was blocked by pretreatment with the selective 5-HT(1A) receptor antagonists N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635), 1-(2-methoxyphenyl)-4-(4-[2-phthalimido]butyl)piperazine (NAN-190) and 4-fluoro-N-(2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl)-N-(2-pyridinyl)benzamide dihydrochloride (p-MPPF), but not by the weak partial agonist/antagonist 8-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-8-azaspiro(4.5)decane-7,9-dione dihydrochloride (BMY 7378). Other 5-HT(1A) receptor agonists (buspirone, gepirone and ipsapirone) also reduced phospho-Erk1/2 levels in hippocampus. 8-OH-DPAT also reduced the levels of the upstream activator of Erk1/2, phosphorylated extracellular signal-regulated kinase kinase (phospho-MEK1/2), and at least one potential downstream target, the nuclear transcription factor phospho-Elk-1. The region- and kinase-specific effects suggest that the Erk1/2 signal transduction cascade is likely an important differential mediator of 5-HT(1A) receptor-regulated events in the central nervous system.
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PMID:5-HT1A receptor-mediated regulation of mitogen-activated protein kinase phosphorylation in rat brain. 1235 65

In the present study we have examined the effects of hydrocarbons on the formation of reactive oxygen species (ROS) in human neutrophil granulocytes in vitro. We found that hydrocarbons induce ROS formation in a concentration-dependent manner and that the ROS-inducing potency increases with increasing number of carbon atoms in the structure. In general, aromatic hydrocarbons were less potent inducers of ROS than aliphatic and cyclic hydrocarbons. The most potent compound in each group, t-butylcyclohexane, n-decane, and n-butylbenzene, were chosen for mechanistic studies. ROS formation was inhibited by the MEK1/2 inhibitor U0126, the tyrosine kinase inhibitor erbstatin-A, and the phosphatidylinositol-3 kinase inhibitor wortmannin. The involvement of the ERK1/2 pathway was confirmed by Western blot analysis of phosphorylated ERK1/2. The study revealed only small differences in the mechanisms involved for the three compounds. The responses were not affected by Pertussis toxin, indicating that Gi-protein coupled receptors are not involved in neutrophil activation after hydrocarbon exposure. Based on these findings we propose a mechanism involving tyrosine kinases, PI3 kinase, and the ERK1/2 pathway, leading to activation of the NADPH oxidase and production of ROS in neutrophils stimulated by organic solvents.
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PMID:Involvement of the extracellular signal regulated kinase pathway in hydrocarbon-induced reactive oxygen species formation in human neutrophil granulocytes. 1287 40

In the aim of beta-carotene biocompatible extraction, toxicity of various pure solvents belonging to different homologous series has been investigated for Dunaliella salina. The results showed that solvents having logP(oct) > 5 or having a molecular weight over 150 g/mol can be considered biocompatible for this microalga. The membrane critical solvent concentration for each series of solvents has been calculated applying Osborne's model, showing that the aliphatic chlorinated hydrocarbon is the most toxic family studied. Mixtures of a biocompatible solvent (decane) with a toxic solvent (CH(2)Cl(2), MEK, MTBE) have been studied. The beta-carotene extraction ability of CH(2)Cl(2)-decane mixture was found six times more efficient than with pure decane. It has been demonstrated that the extraction ability of solvent depends on its affinity with the product extracted and on its concentration incorporated in the cellular membrane.
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PMID:Optimal selection of organic solvents for biocompatible extraction of beta-carotene from Dunaliella salina. 1815 12