Regulation of lipoxygenase activity by polyunsaturated lysophosphatidylcholines or their oxygenation derivatives.

Lysophosphatidylcholines (lysoPCs) have been known to play a role as lipid mediators in various cellular responses. In this study, we examined whether lysoPC containing linoleoyl, arachidonoyl, or docosahexaenoyl groups or their peroxy derivatives affect lipoxygenase (LOX)-catalyzed oxygenation of native substrates. First, arachidonoyl lysoPC and docosahexaenoyl lysoPC were found to inhibit potato 5-LOX-catalyzed oxygenation of linoleic acid (LA) in a noncompetitive type with Ki values of 0.38 and 1.90 microM, respectively. Likewise, arachidonoyl lysoPC and docosahexaenoyl lysoPC also inhibited 5-LOX activity from rat basophilic leukemia cells-2H3 (RBL-2H3) with IC50 values (50% inhibitory concentration) of 18.5 +/- 3.06 and 30.6 +/- 1.06 microM, respectively. Additionally, arachidonoyl lysoPC and docosahexaenoyl lysoPC also inhibited 15-LOX activity from RBL-2H3 with IC50 values of 16.6 +/- 1.3 and 24.1 +/- 2.4 microM, respectively. In a separate experiment, where lysoPC peroxides were tested for the effect on soybean LOX-1, 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoyl lysoPC and 17(S)-hydroperoxy-4,7,10,13,15,19-docosahexaenoyl lysoPC potently inhibited soybean LOX-1 activity with Ki values of 6.8 and of 1.54 microM, respectively. In contrast, 13(S)-hydroperoxy-9,11-octadecadienoyl lysoPC was observed to stimulate soybean LOX-1-catalyzed oxygenation of LA markedly with AC50 value (50% activatory concentration) of 1.5 microM. Taken together, it is proposed that lysoPCs containing polyunsaturated acyl groups or their peroxy derivatives may participate in the regulation of LOX activity in biological systems.