linoleic-acid and 1-oleoyl-2-acetylglycerol

Linoleic acid has been shown to inhibit melanogenesis in cultured B16 mouse melanoma cells. We report here the possible involvement of protein kinase C (PKC) in linoleic acid-induced inhibition of melanogenesis in B16 cells. A single PKC subspecies (alpha-PKC) was detected in B16 cells. The enzyme was activated by linoleic acid in vitro. The effective concentrations at which PKC was activated (25 microM; maximum response) were consistent with those for the inhibition of melanogenesis in cell culture system. In addition, the permeable diacylglycerol 1-oleoyl-2-acetyl glycerol that activates PKC also inhibits melanogenesis at 100 microM. These results suggest that activation of PKC plays a pivotal role in the linoleic acid-induced inhibition of melanogenesis in B16 cells.

Topics: Animals; Diglycerides; Enzyme Activation; Linoleic Acid; Linoleic Acids; Melanins; Melanoma, Experimental; Mice; Protein Kinase C; Tumor Cells, Cultured

Thrombin, 1-oleoyl-2-acetyl-rac-glycerol (OAG), cis- or trans-octadecadienoic acids (linoleic and linolelaidic acid) and the synergistic combination of octadecadienoic acids plus OAG lead to the activation of gel-filtered human platelets, i.e. aggregation via protein kinase C (PKC). Platelet activation by thrombin was only slightly suppressed by polymyxin B, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) or staurosporine, all being potent inhibitors of PKC in vitro. The OAG-induced aggregation, however, was strongly inhibited by H-7 or staurosporine but not by polymyxin B. In contrast, octadecadienoic acid-induced aggregation was substantially inhibited only by polymyxin B. Synergistic activation by OAG plus octadecadienoic acids was strongly suppressed by all three PKC inhibitors. Our results indicate (1) that the ability of various compounds to inhibit PKC in vitro does not correlate with their inhibitory effects in intact cells and (2) that platelet activation induced by various PKC activators exhibits differential PKC-inhibitor sensitivity.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Alkaloids; Diglycerides; Humans; Isoquinolines; Linoleic Acid; Linoleic Acids; Male; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymyxin B; Polymyxins; Protein Kinase C; Staurosporine; Thrombin