Regulation of neutral cholesteryl esterase in arterial smooth muscle cells: stimulation by agonists of adenylate cyclase and cyclic AMP-dependent protein kinase.
Cultured arterial smooth muscle cells have been found to contain an activatable neutral cholesteryl esterase (EC 3.1.1.13). This enzyme is similar to that previously described in adipose tissue, adrenal cortex, and aortic homogenates. Although both the lysosomal (acid) and cytoplasmic (neutral) cholesteryl esterases were activated two- to threefold by the addition of 100 microM dibutyryl cyclic AMP, only neutral cholesteryl esterase was responsive to 100 microM dibutyryl cyclic AMP, 10 mM MgATP, and 50 micrograms/ml exogenous protein kinase when added together. Protein kinase inhibitor (10 micrograms/ml) reversed the action of cyclic AMP-dependent protein kinase; deactivation of neutral cholesteryl esterase was also shown to occur with 50 micrograms/ml phosphoprotein phosphatase. In addition, 0.2 microM prostacyclin, 50 microM forskolin, and an agonist of the beta-adrenergic receptor, 5 microM isoproterenol, significantly stimulated intracellular cyclic AMP accumulation and activated cholesteryl esterase in arterial smooth muscle cells. The data indicate that neutral cholesteryl esterase in arterial smooth muscle cells can be modulated by a phosphorylation-dephosphorylation system involving the cyclic AMP-dependent protein kinase-phosphoprotein phosphatase. Regulation of cholesteryl esterase by this mechanism may affect lipid accumulation in these arterial cells.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003593:Cytoplasm / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D050356:Lipid Metabolism; D008247:Lysosomes / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology
D013565:Sympatholytics; D013566:Sympathomimetics; D011494:Protein Kinases; D002265:Carboxylic Ester Hydrolases; D002787:Sterol Esterase; D010749:Phosphoprotein Phosphatases; D000262:Adenylyl Cyclases