Effects of docosahexaenoic and arachidonic acids on the synthesis and distribution of aminophospholipids during neuronal differentiation of PC12 cells

We have shown previously that docosahexaenoic acid (DHA) promotes and arach idonic acid (AA) suppresses neurite outgrowth of PC12 cells induced by nerv e growth factor (NGF) and that incorporation of [H-3]ethanolamine into phos phatidylethanolamine (PE) is suppressed in PC12 cells by AA while DHA has n o effect. In the present study, the effects of these fatty acids on PE synt hesis via decarboxylation of phosphatidylserine (PS), another pathway of PE synthesis, and distribution of aminophospholipids were examined. Incorpora tion of [H-3]serine into PS and PE was elevated in the course of NGF-induce d differentiation and was further stimulated significantly by DHA, but not by Ak [H-3]Ethanolamine uptake by PC12 cells was significantly suppressed b y AA but not by DHA while these fatty acids did not affect [H-3]serine upta ke, indicating that the suppression by Ak of [H-3]ethanolamine incorporatio n into phosphatidylethanolamime is attributable, at least in part, to a red uction in [H-3]ethanolamine uptake. The distribution of PE in the outer lea flet of plasma membrane decreased during differentiation, which is known to be accompanied by an increase in the surface area of plasma membrane. Supp lementation of PC12 cells with DHA or AA did not affect the distribution of aminophospholipids. Thus, DHA and AA affected aminophospholipid synthesis and neurite outgrowth differently, but not the transport and distribution o f aminophospholipids, while the PE concentration in the outer leaflet of th e plasma membrane decreased in association with morphological changes in PC 12 cells induced by NGF. (C) 1999 Academic Press.