title: Potentiation of diacylglycerol-activated protein kinase C by acyl-coenzyme A thioesters of hypolipidaemic drugs.
abstract: Acyl-Coenzyme A thioesters of the hypolipidaemic and cancerinogenic peroxisome proliferators clofibric acid, nafenopin, ciprofibrate, bezafibrate and tibric acid were found to greatly increase the activity of rat brain protein kinase C. Maximal activation required the simultaneous presence of Ca+2, phosphatidylserine and diolein, thus differentiating their action from that of other tumor promoters such as phorbol esters. Under similar conditions the unesterified drugs were comparatively ineffective. Similar results were obtained using the rat liver enzyme. The data suggest that acylcoenzyme A thioesters of hypolipidaemic drugs, may play a role in the induction of liver tumors by these compounds, through the potentiation of protein kinase C.
authors.affiliation: Faculty of Biological Sciences, P. Universidad Catolica de Chile, Santiago.
authors.forename: M
authors.initials: M
authors.lastname: Bronfman
authors.forename: A
authors.initials: A
authors.lastname: Orellana
authors.forename: M N
authors.initials: MN
authors.lastname: Morales
authors.forename: F
authors.initials: F
authors.lastname: Bieri
authors.forename: F
authors.initials: F
authors.lastname: Waechter
authors.forename: W
authors.initials: W
authors.lastname: Stäubli
authors.forename: P
authors.initials: P
authors.lastname: Bentley
mesh_terms: D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004075:Diglycerides / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007700:Kinetics; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
chemical_list: D000214:Acyl Coenzyme A; D004075:Diglycerides; D000960:Hypolipidemic Agents; D011493:Protein Kinase C