Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide

Yuan Soon Ho, Hung Bin Liou, Jen Kun Lin, Jiiang Huei Jeng, Min Hsiung Pan, Yu Ping Lin, How Ran Guo, Sheng Yow Ho, Ching Chang Lee, Ying Jan Wang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Nitric oxide (NO) is an environmental pollutant found in smog and cigarette smoke. Recently, NO has been discovered to act as a molecular messenger, mediating various physiological functions. However, when an excess of NO is present, cytotoxic and mutagenic effects can also be induced. The reaction of NO with superoxide results in the formation of peroxynitrite (ONOO-), which decomposes into the hydroxyl radical and nitrogen dioxide. Both of them are potent oxidant species that may initiate and propagate lipid peroxidation. In the present study, we examined the effects of NO and ONOO- on the induction of lipid peroxidation and cell death mechanisms in rats and in A549 pulmonary epithelial cells. The results showed that ONOO- is able to induce lipid peroxidation in pulmonary epithelial cells in a dose-dependent manner. 8-Epi-prostaglandin F can serve as a good biomarker of lipid peroxidation both in vitro and in vivo. Postmitotic apoptosis was found in A549 cells exposed to NO, whereas ONOO- induced cell death more characteristic of necrosis than apoptosis. Apoptosis that occurred in cells may be related to the dysfunction of mitochondria, the release of cytochrome c into cytosol, and the activation of caspase-9. The relationship between caspase activation and the cleavage of other death substrates during postmitotic apoptosis in A549 cells needs further investigation.

Original languageEnglish
Pages (from-to)484-493
Number of pages10
JournalArchives of Toxicology
Volume76
Issue number8
DOIs
Publication statusPublished - 2002

    Fingerprint

Keywords

  • Apoptosis
  • Lipid peroxidation
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Ho, Y. S., Liou, H. B., Lin, J. K., Jeng, J. H., Pan, M. H., Lin, Y. P., Guo, H. R., Ho, S. Y., Lee, C. C., & Wang, Y. J. (2002). Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide. Archives of Toxicology, 76(8), 484-493. https://doi.org/10.1007/s00204-002-0373-3