Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arachidonic acid (AA), a metabolite of membrane phospholipids, and its metabolites are increased in Mg2+ deficiency. We examined whether the extracellular Mg2+ concentration affects AA production and whether AA regulates a putative Na+-dependent Mg2+ efflux pathway in renal epithelial NRK-52E cells. We used the cells cultured in 5 mM Mg2+-containing medium for 2 days because they enable us to detect Na+-stimulated Mg2+ efflux that was not observed in normal culture medium. Removal of extracellular Mg2+ increased AA release both in the absence and presence of extracellular Na+. This was inhibited by methyl arachidonyl fluorophosphonate (MAFP, 10 microM), an inhibitor of cytosolic phospholipase A) (cPLA2) and Ca2+-independent phospholipase A2 (iPLA2), and bromoenol lactone (BEL, 10 microM), an inhibitor of iPLA2. However, LY-311727 (10 microM), a secretory phospholipase A2 (sPLA2) inhibitor, had no inhibitory effect. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that NRK-52E cells express cPLA2 and iPLA2 mRNAs, but not sPLA2. In the mag-fura 2 fluorescence measurements, extracellular Mg2+ removal caused slight decrease in the intracellular free Mg2+ concentration ([Mg2+]i) in the Na+-free condition. The addition of Na+ caused a rapid decrease in [Mg2+]i, indicating the presence of a Na+-dependent Mg2+ efflux pathway. The Na+-dependent [Mg2+]i decrease was suppressed by MAFP and BEL. On the other hand, AA metabolite inhibitors, nordihydroguaiaretic acid (NDGA) (50 microM), indomethacin (10 microM) and 17-octadecynoic acid (ODYA) (10 microM), enhanced the Na+-dependent [Mg2+]i decrease. Furthermore, the addition of exogenous AA (30 microM) enhanced the Na+-dependent [Mg2+]i decrease, which was significantly inhibited by imipramine (0.1 mM), a putative Na+/Mg2+-exchanger inhibitor. These results suggest that extracellular Mg2+ removal elevates AA release mediated mainly by iPLA2 and that AA upregulates the Na+-dependent Mg2+ efflux in NRK-52E cells.
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PMID:Arachidonic acid-activated Na+-dependent Mg2+ efflux in rat renal epithelial cells. 1464 27

Previously we have shown that dietary conjugated linoleic acid (CLA) significantly decreased colon tumor incidence in rats injected with 1,2-dimenthylhydrazine (DMH). The present study was performed to explore the mechanisms responsible for the anticarcinogenic effect of CLA. Four groups of rats received either vehicle or intramuscular injections of DMH at the dose of 15 mg/kg body weight twice per week for 6 weeks and were fed a diet containing either 0% or 1.0% CLA ad libitum for 14 weeks. Dietary CLA decreased cellular proliferation and induced apoptosis in the colonic mucosa of both vehicle and DMH-treated rats. Mucosal levels of prostaglandin (PG) E(2), thromboxane B(2), and 1,2-diacylglycerol decreased in rats fed the 1% CLA diet, whereas cyclooxygenase-2 levels were not affected. Arachidonate content of mucosal phospholipids decreased significantly in rats fed the 1% CLA diet. Reverse transcriptase-polymer chain reaction analysis revealed that the Bax/Bcl-2 transcript ratio was significantly increased in rats fed 1% CLA. To examine whether the 1% CLA diet reduces tumor incidence, the DMH-treated rats were continuously fed the assigned diets for 30 weeks. Tumor incidence was significantly decreased in the CLA-fed group. In conclusion, our findings are consistent with the hypothesis that CLA decreases the incidence of colon cancer by decreasing cellular proliferation and inducing apoptosis of the colonic mucosa. These effects may be due in part to decreased PGE(2) levels and increased Bax/Bcl-2 ratios.
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PMID:Dietary conjugated linoleic acid increases the mRNA ratio of Bax/Bcl-2 in the colonic mucosa of rats. 1506 16

Insulin secretion from pancreatic beta cells is partly regulated by cell membrane potential. Background K+ channels that stabilize the resting membrane potential would suppress excitability and insulin secretion. Recent studies show that members of the two-pore domain K+ (K2P) channel family behave as background K+ channels in many excitable cells. Therefore, the expression of K2P channels was studied in insulin-secreting MIN6 cells. Reverse transcriptase PCR showed that, among nine K2P channels tested, TASK-1, TASK-2, TASK-3, TREK-2, and TRESK-2 were expressed in MIN6 cells. Cell-attached recordings on MIN6 cells revealed five types of K+ channels that were open at rest. Two were ATP-sensitive and Ca2+-activated K+ channels, as judged by their sensitivity to ATP and Ca2+, respectively, and single-channel conductance. Among five K2P channels, only TREK-2 could be clearly identified in MIN6 cells. The molecular identity of two other K+ channels is not yet known. TREK-2 in MIN6 cells was activated by arachidonic acid, membrane stretch, and low pH solution (pH 5.8). Arachidonic acid increased Ba2+-sensitive whole-cell current in MIN6 cell. These results suggest that TREK-2 contributes to the background K+ conductance in MIN6 cells, and may regulate depolarization-induced secretion of insulin.
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PMID:Functional expression of TREK-2 in insulin-secreting MIN6 cells. 1535 40