title: Mechanisms of cell death induced by nitric oxide and peroxynitrite in Calu-1 cells.
abstract: S-nitrosoglutathione (GSNO) is an important physiological redox form of nitric oxide (NO) and serves as an NO-releasing compound. 3-Morpholinosydnonimine hydrochloride (SIN-1) produces NO and superoxide anion (O(2)(·-)) which results in the formation of peroxynitrite (ONOO(-)). We investigate the cytotoxicity, cell death mechanisms and gene expression of NO and ONOO(-) in human lung epithelial cells show NO induced apoptosis and DNA genomic fragmentation. Whereas, ONOO(-) induced cell death more characteristic of necrosis than apoptosis. The concentrations of GSNO and SIN-1 required to cause death in 50% of cells were greater than 1 mM. Several gene products are important in controling the apoptotic and necrotic processes. Of these, bcl-2, bax and hsp 70 were studied. The level of expression of bcl-2 was dramatically decreased in cells treated with SIN-1 or GSNO, while the expression level of bax, the heterodimer of bcl-2, did not significant change. In addition, a roughly two-fold increase of hsp 70 was found in cells treated with SIN-1. There were no significant changes in hsp 70 levels in cells treated with GSNO.
authors.affiliation: Institute of Biochemistry, College of Medicine, National Taiwan University, No. 1, Section. 1, Jen-ai Road, Taipei, Taiwan, ROC.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Wang
authors.forename: Y S
authors.initials: YS
authors.lastname: Ho
authors.forename: M H
authors.initials: MH
authors.lastname: Pan
authors.forename: J K
authors.initials: JK
authors.lastname: Lin