Nitric oxide-induced activation of NF-κB-mediated NMDA-induced CTP:phosphocholine cytidylyltransferase alpha expression inhibition in A549 cells

Pulmonary surfactant is a lipoprotein complex on the alveolar surface. It reduces the surface tension at the air-water interface and stabilizes the alveoli during expiration. Surfactant deficiency or dysfunction is associated with occurrence and development of many pulmonary diseases. Family members of CTP:phosphocholine cytidylyltransferase are rate-limiting enzymes for surfactant phospholipid synthesis. We had reported recently that the expression of CTP:phosphocholine cytidylyltransferase alpha (CCT-alpha) was inhibited during N-methyl-d-aspartic acid (NMDA)-induced lung injury. But the molecular mechanism underlining remains elusive. In this work, we reported that NMDA induced nitric oxide synthase (NOS) activation and nuclear factor-kB (NF-kappa B) subunit p65 nuclear translocation in A549 cells, which were responsible for decreased (CCT-alpha) expression. Furthermore, NOS activation and elevated NO production are upstream regulators for p65 nuclear translocation and (CCT-alpha) expression inhibition. Our results provided important clues for further elucidating the mechanisms underlying glutamate-induced lung injury.