DIFFERENTIAL ALTERATIONS OF ETHANOLAMINE AND CHOLINE PHOSPHOGLYCERIDEMETABOLISM BY CLOFIBRATE AND RETINOIC ACID IN HUMAN FIBROBLASTS ARE NOT MEDIATED BY PHORBOL ESTER-SENSITIVE PROTEIN-KINASE-C

Peroxisomal proliferators and retinoids have been reported to interact to regulate lipid metabolism, particularly beta-oxidation of fatty ac ids. Based on postulated interac tions of these agents at the levels o f receptors and response elements, we examined whether interactions ex ist between the peroxisomal proliferator, clofibrate (CLF), and retino ic acid (RA) in modulation of phospholipid turnover in cultured human skin fibroblasts. Treatment of cultured cells with either 25 mu M CLF or 1 mu M RA alone decreased [C-14]ethanolamine incorporation into eth anolamine phosphoglycerides (EPG) by 20-30%, and simultaneous exposure to both agents resulted in additive inhibition. By contrast, [H-3]cho line incorporation into phospholipid was stimulated 5-30% by incubatio n with either agent; when CLF and RA were administered together, the s timulatory effects were additive. Different types of pulse-chase studi es examining effects on uptake, biosynthesis, and degradation of label led phospholipids indicated stimulation of EPG degradation and inhibit ion of phosphatidylcholine degradation by CLF; no effect on catabolism of either phospholipid was observed with RA. Combinations of modifier s of protein kinase activity [4 beta-2-O-tetradecanoylphorbol-13-aceta te (beta-TPA), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydroch loride, N-(2'-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride, bis-indolylmaleimide, staurosporine] indicated that beta-TPA-responsi ve protein kinases were not involved. Accordingly, CLF and RA regulate biosynthesis and degradation of ethanolamine and choline phosphoglyce rides in cultured skin fibroblasts by different mechanisms that do not involve classical protein kinase C (PKC) isoforms, even though turnov er of phospholipids generating lipid activators of PKC occurs.