SUBSTITUTION OF 15(S)HYDROXYEICOSATETRAENOIC ACID IN PHOSPHATIDYLINOSITOL ALTERS THE GROWTH OF LIVER EPITHELIAL-CELLS

We investigated the substitution of 15(S)-hydroxyeicosatetraenoic acid (15(S)HETE) in phospholipid signalling pathways and its consequences on the growth of non-transformed (NT-) and spontaneously transformed ( T-) rat liver epithelial cells (RLEC). 15(S)HETE was selectively incor porated into the sn-2 position of phosphatidylinositol (PI) and at a h igher rate into T-RLEC. RLEC rapidly mobilized the resulting 15(S)HETE -containing PI (IS(S)HETE-PI) and produced 1-acyl,2-[15(S)HETE]-glycer ol. Although total diacylglycerol levels were similar in both cell typ es, the ratio 1-acyl,2-[15(S)HETE]-glycerol/15(S)HETE-PI was higher in NT-RLEC, suggesting a lower mobilization of IS(S)HETE-PI in T-RLEC. U sing rat brain protein kinase C, 1-stearoyl,2-[15(S)HETE]-glycerol was as potent an in vitro protein kinase C activator as 1-stearoyl,2-arac hidonoyl-glycerol. Finally, selective substitution of 15(S)HETE in PI altered DNA synthesis in T-RLEC: whereas low concentrations of 15(S)HE TE (1 nM and 10 nM) in these cells were mitogenic, higher concentratio ns resulted in a 30 % inhibition of DNA synthesis.