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.
Li
Lian
L
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
Shen
Li
L
She
Hua
H
Yue
Shaojie
S
Feng
Dandan
D
Luo
Ziqiang
Z
D019916:Choline-Phosphate Cytidylyltransferase / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019916:Choline-Phosphate Cytidylyltransferase; C517213:PCYT1A protein, human