Lysophosphatidylcholine: a signal for neuronal differentiation in Neuro-2a cells

PAOLETTI, LUCIANA; DOMIZI, P; BANCHIO, C

Rosario

Congreso; Sociedad Argentina de Bioquímica y Biología Molecular; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian membranes, and its biosynthesis is required in several processes like neuronal differentiation. We use Neuro-2a cells that can be induced to differentiate by treatment with Retinoic Acid (RA). We previously demonstrated that stable cell lines that overexpressed enzymes involved in the biosynthesis of PC undergo neuronal differentiation in the absence of RA, suggesting a regulatory role of PC metabolism. We demonstrated that addition of PC liposomes promotes neuronal differentiation, and that this process depend on cytoplasmatic phospholipase A2 (cPLA2) activity. As a consequence, we observed that lysophosphatidylcholine (LPC) but not fatty acids induce neuronal differentiation. LPC promote the process by activating ERK cascade. Experiments of supplementation with lysophosphatidic acid showed that this lysophospholipid is unable to induce differentiation. However, the addition of 1-O-palmityl-sn-glycero-3-phosphocholine (LPAF, which has an ether bond in the 1-position that prevents its hydrolysis) exert the same effect that LPC. The pharmacological inhibition of LPC acyltransferase (a condition that increases the level of endogenous LPC) showed an induction of neuronal differentiation even in the absence of RA. The results suggest that LPC is a neurotrophin-like factor able to promote neuronal differentiation.