Selective inhibition of choline kinase or CTP:phosphocholine cytidylyltransferase alpha impairs neuronal differentiation induced by retinoic acid stimulation.

ELENA, CLAUDIA; BANCHIO, CLAUDIA

Congreso; XLVI Reuniona Anual- Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2010

SAIB

Neuronal differentiation implies an increase in cell membrane phospholipids in order to face the demand for neurite outgrowth. In Neuro2A cell line, retinoic acid (RA) induced differentiation is driven by MAP kinase signalling and promotes an increase in phosphatidylcholine (PtdCho) synthesis. In this way, coordinated transcriptional and post-translational mechanisms are involved in the sequential activation of two of the key enzymes of the Kennedy pathway: CCTa biochemical activation, CK mRNA stabilization, and an enhanced expression of both of these genes. The aim of this study is to further characterize the role of CK and CCTa in the neuronal differentiation process. Selective inhibition of these enzimes using siRNA approaches, significantly abrogates the extension of neurites. Moreover, the use of pharmacological inhibitors of CK or CCTa, produces a reduction in the percentage of differentiated neuronal cells after RA stimulation. According to these results, the decrease in phosphatydilcholine or its derivatives may alter the production of lipids second messengers which could modify signalling cascades involved in neuronal differentiation