Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide.
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(2)(alpha) 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.
Ho
Yuan-Soon
YS
School of Medical Technology, Taipei Medical University, Taipei, Taiwan.
Liou
Hung-Bin
HB
Lin
Jen-Kun
JK
Jeng
Jiiang-Huei
JH
Pan
Min-Hsiung
MH
Lin
Yu-Ping
YP
Guo
How-Ran
HR
Ho
Sheng-Yow
SY
Lee
Ching-Chang
CC
Wang
Ying-Jan
YJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D028441:F2-Isoprostanes / Q000652:urine; D006801:Humans; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D015227:Lipid Peroxidation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D028441:F2-Isoprostanes; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D020169:Caspases