Phospholipids induce neuronal differentiation in Neuro-2a cells.

PAOLETTI L., DOMIZI P. Y BANCHIO C.

Buenos Aires

Congreso; Sociedad Argentina de Bioquímica y Biología Molecular- Molecular mechanisms in cell signaling and gene expression; 2013

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Phosphatidylcholine (PC), the most abundant phospholipid in membranes of eukaryotic cells, is induced in different processes that require membrane biosynthesis. Retinoic acid (RA) induced differentiation of neuroblastoma cells is an example of this, and we demonstrated that PC and its derivative metabolites are not only important as structural membrane building blocks, but could be involved in the signalling and stimulation of pathways driving neuronal differentiation. The addition of PC liposomes promotes neuronal differentiation without inducer (RA) and induces PC biosynthesis, mimicking the RA effects. We found that PC-induced differentiation requires activation of ERK pathway and this process is dependent on citoplasmatic phospholipase A2 activity (cPLA2). Supplementation of medium with intermediates of PC synthesis (Choline, P-Cho and CDP-Cho) and PC derivative metabolites (lysophosphatidylcholine (LPC) and phosphatidic acid) induce neuritogenesis, but not lysophosphatidic acid and arachidonic acid. The treatment with different phospholipase inhibitors demonstrated that neuronal differentiation requires cPLA2 activity, suggesting that LPC could be the signal that triggers this process. The other metabolites would induce PC biosynthesis and produce LPC through cPLA2 activity.