Activation of a thioesterase specific for very-long-chain fatty acids by adrenergic agonists in perfused hearts

We have recently described an acyl-CoA thioesterase specific for very-long- chain fatty acids, named ARTISt, that regulates steroidogenesis through the release of arachidonic acid in adrenal zona fasciculata cells. In this pap er we demonstrate the presence of the protein as a 43 kDa band and its mRNA in cardiac tissue. The activity of the protein was measured using an heter ologous cell-free assay in which it is recombined with adrenal microsomes a nd mitochondria to activate mitochondrial steroidogenesis. Isoproterenol an d phenylephrine activate the enzyme in a dose-dependent manner (10(-10)-10( -6) M). Both propranolol (10(-5) M) and prazosin (10(-5) M) block the actio n of isoproterenol and phenylephrine respectively. Antipeptide antibodies a gainst the serine lipase motif of the protein and the Cys residue present i n the catalytic domain also block the activity of the protein. Taken togeth er, our results confirm the presence of ARTISt in heart and provide evidenc e for a catecholamine-activated regulatory pathway of the enzyme in that ti ssue. (C) 1999 Elsevier Science B.V. All rights reserved.