Angiogenin activates phospholipase C and elicits a rapid incorporation of fatty acid into cholesterol esters in vascular smooth muscle cells.
Angiogenin activates the phosphoinositide-specific phospholipase C (PLC) in cultured rat aortic smooth muscle cells to yield a transient (30 s) peak of 1,2-diacylglycerol (DG) and inositol trisphosphate. Within 1 min, the DG level falls below that of the control and remains so for at least 20 min. A transient increase in monoacylglycerol indicates that depletion of DG may be the consequence of hydrolysis by DG lipase. In addition to these changes in second messengers, a rapid increase in incorporation of radiolabeled tracer into cellular cholesterol esters is observed. Stimulated cholesterol ester labeling is inhibited by preincubation with either the DG lipase inhibitor RHC 80267 or the acyl coenzyme A:cholesterol acyltransferase inhibitor Sandoz 58035. Cells prelabeled with [3H]arachidonate show a sustained increase in labeling of cholesterol esters following exposure to angiogenin. In contrast, cells prelabeled with [3H]oleate show only a transient elevation that returns to the basal level by 5 min. This suggests initial cholesterol esterification by oleate followed by arachidonate that is released by stimulation of the PLC/DG lipase pathway.
Moore
F
F
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts 02115.
Riordan
J F
JF
D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000096:biosynthesis*; D006224:Cricetinae; D004075:Diglycerides / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005989:Glycerides / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012259:Ribonuclease, Pancreatic; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
D002788:Cholesterol Esters; D004075:Diglycerides; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005989:Glycerides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D011506:Proteins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D010738:Type C Phospholipases