Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the polyunsaturated fatty acid cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) on the high-affinity, sodium-dependent uptake of D-[3H]aspartate into purified rat brain synaptosomes was examined. Incubation of the synaptosomes with 20 microM DHA caused over 50% inhibition of the maximum velocity (V(max)) of D-[3H]aspartate transport. This inhibition was significantly potentiated by pre-exposure of the synaptosomes to the fatty acid for 10 min prior to the start of the transport assay. Less highly unsaturated fatty acids such as arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid), linolenic acid (cis-9,12,15-octadecatrienoic acid) and oleic acid (cis-9-octadecenoic acid) were significantly less potent than DHA. Removal of extracellular calcium, or reduction of the intracellular calcium concentration using the intracellular calcium chelator BAPTA/AM (10 microM), did not reduce the inhibition caused by DHA. On the other hand, an increase in the concentration of intracellular calcium mediated by thapsigargin (25 microM) or the calcium ionophore A23187 (10 or 100 nM) led to a reduction in the rate of D-[3H]aspartate transport in the absence of DHA. The CaM kinase II inhibitor, KN-93, reduced D-[3H]aspartate uptake independently of whether DHA was also present, but had no effect on the inhibition of D-[3H]aspartate uptake by either A23187 or thapsigargin. We conclude that whereas DHA inhibits synaptosomal D-[3H]aspartate uptake in a calcium-independent manner, a calcium-based mechanism exists that can also modulate glutamate transporter activity.
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PMID:An investigation into the role of calcium in the modulation of rat synaptosomal D-[3H]aspartate transport by docosahexaenoic acid. 1272 59

Angiotensin II (ANG II) promotes vascular smooth muscle cell (VSMC) growth, stimulates Ca(2+)-calmodulin (CaM)-dependent kinase II (CaMKII), and activates cytosolic Ca(2+)-dependent phospholipase A2 (cPLA2), which releases arachidonic acid (AA). ANG II also generates H2O2 and activates Akt, which have been implicated in ANG II actions in VSMC. This study was conducted to investigate the relationship of these signaling molecules to Akt activation in rat aortic VSMC. ANG II increased Akt activity, as measured by its phosphorylation at serine-473. ANG II (200 nM)-induced Akt phosphorylation was decreased by extracellular Ca2+ depletion and calcium chelator EGTA and inhibitors of CaM [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] and CaMKII [(2-[N-(2-hydroxyethyl)]-N-(4-me-thoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzyl-amine)]. cPLA2 inhibitor pyrrolidine-1, antisense oligonucleotide, and retroviral small interfering RNA also attenuated ANG II-induced Akt phosphorylation. AA increased Akt phosphorylation, and AA metabolism inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) blocked ANG II- and AA-induced Akt phosphorylation (199.03 +/- 27.91% with ANG II and 110.18 +/- 22.40% with ETYA + ANG II; 405.00 +/- 86.22% with AA and 153.97 +/- 63.26% with ETYA + AA). Inhibitors of lipoxygenase (cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate) and cytochrome P-450 (ketoconazole and 17-octadecynoic acid), but not cyclooxygenase (indomethacin), attenuated ANG II- and AA-induced Akt phosphorylation. Furthermore, 5(S)-, 12(S)-, 15(S)-, and 20-hydroxyeicosatetraenoic acids and 5,6-, 11,12-, and 14,15-epoxyeicosatrienoic acids increased Akt phosphorylation. Catalase inhibited ANG II-increased H2O2 production but not Akt phosphorylation. Oleic acid, which also increased H2O2 production, did not cause Akt phosphorylation. These data suggest that ANG II-induced Akt activation in VSMC is mediated by AA metabolites, most likely generated via lipoxygenase and cytochrome P-450 consequent to AA released by CaMKII-activated cPLA2 and independent of H2O2 production.
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PMID:Angiotensin II-induced Akt activation is mediated by metabolites of arachidonic acid generated by CaMKII-stimulated Ca2(+)-dependent phospholipase A2. 1563 21