DIFFERENTIAL REGULATION OF HUMAN T-LYMPHOCYTE PROTEIN-KINASE-C ACTIVITY BY UNSATURATED FATTY-ACIDS

Administration of gamma-linolenic acid suppresses active synovitis in patients with rheumatoid arthritis. We therefore examined the effects of gamma-linolenic acid and its first metabolite, dihomo-gamma-linolen ic acid, on protein kinase C, a key element in transduction of signals from cell surface to nucleus. We report here that gamma-linolenic aci d and dihomo-gamma-linolenic acid suppress total protein kinase C acti vity, but facilitate translocation of protein kinase C activity from c ytosol to membrane in human peripheral blood T lymphocytes stimulated with phorbol 12-myristate 13-acetate. Arachidonic acid and eicosapenta enoic acid do not influence total protein kinase C activity and have o nly modest effects on enzyme translocation. These findings in whole ce lls are in contrast to results of experiments performed with isolated protein kinase C, in which unsaturated fatty acids uniformly enhance p rotein kinase C activity, The differential effects of unsaturated fatt y acids underscore the complexity of protein kinase C regulation and i ndicate that gamma-linolenic and dihomo-gamma-linolenic acids influenc e T lymphocyte protein kinase C metabolism in a manner that is unique among unsaturated fatty acid precursors of eicosanoids. (C) 1995 Acade mic Press, Inc.