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

Abstract

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.

• Authors: Lian Li, Li Shen, Hua She, Shaojie Yue, Dandan Feng, Ziqiang Luo
• Journal: Cell biology and toxicology (Cell Biol Toxicol) Vol. 27 Issue 1 Pg. 41-7 (Feb 2011) ISSN: 1573-6822 [Electronic] Netherlands
• PMID: 20661636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Nitric Oxide
• N-Methylaspartate
• Choline-Phosphate Cytidylyltransferase
• PCYT1A protein, human

Topics

• Choline-Phosphate Cytidylyltransferase (biosynthesis)
• Gene Expression Regulation, Enzymologic
• Humans
• N-Methylaspartate (pharmacology)
• NF-kappa B (physiology)
• Nitric Oxide (physiology)
• Signal Transduction
• Tumor Cells, Cultured