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-α) 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–κB) subunit p65 nuclear translocation in A549 cells, which were responsible for decreased (CCT-α) expression. Furthermore, NOS activation and elevated NO production are upstream regulators for p65 nuclear translocation and (CCT-α) expression inhibition. Our results provided important clues for further elucidating the mechanisms underlying glutamate-induced lung injury.
KeywordsNMDA NF–κB CCT-α
We would like to thank Ms. Huijun Liu for technical assistance and Dr. Suzanne Jackowski for CCT-α antibody. This work was supported by grants (Nos. 30370531, 30471835) from National Natural Science Foundation of China (to Z.L.).
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