ROLE OF PHOSPHATIDYLCHOLINE BIOSYNTHESIS ON NEURONAL DIFFERENTIATION

MALIZIA, F, MONTANER ANELEY, ELENA, C AND BANCHIO C

Cordoba

Congreso; SAIB; 2016

Role of phosphatidylcholine biosynthesis on neuronal differentiation. Malizia, F.; Montaner, A.; Elena, C.; Banchio, C.IBR-CONICET, Ocampo y Esmeralda, Rosario, ArgentinaE-mail: flormalizia@gmail.comNeuronal differentiation implies an increase in membrane phospholipids in order to face the demand for neurites outgrowth. As phosphatidylcholine (PtdCho) is the major component of mammalian membranes, its biosynthesis plays a key role during neuronal differentiation. Interestingly, increased PtdCho biosynthesis not only provides structural components for neurite developing, but also plays an active role in regulating neuronal differentiation in Neuro-2a cells and in embryonic neural stem cells (NSCs). In Neuro-2a cells, retinoic acid (RA) and lisophosphatidylcholine (LPtdCho) promote neuronal differentiation by activating the MAPKK pathway. They also promote an increase in PtdCho synthesis by adapting the expression and activity of choline kinase alpha (CK and CTP-phosphocholine cytidylyltransferase alpha (CCT. In addition, it has been reported that in PC12 cells CCT isoform regulates neurite branching. The aim of this study is to analyze the effect that inhibition of CKCCT and CCT caused on Neuro-2a and NSCs differentiation. We demonstrated that, before the induction with RA and LPtdCho, the selective inhibition of these enzymes by siRNA and by pharmacological approaches impaired neuronal differentiation of Neuro-2a cells. Moreover, pharmacological inhibition of CK and CCT in NSCs caused a reduction in neurites length.