TY - JOUR
T1 - Mechanisms of cell death induced by nitric oxide and peroxynitrite in Calu-1 cells
AU - Wang, Ying Jan
AU - Ho, Yuan Soon
AU - Pan, Min Hsiung
AU - Lin, Jen Kun
N1 - Funding Information:
This study was supported by the National Science Council (NSC 86-2621-B-002-008-Z) and by the National Health Research Institute (DOH-86-HR-403, 86-06).
PY - 1998/8/4
Y1 - 1998/8/4
N2 - 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 (O2.-) 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 bar, 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.
AB - 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 (O2.-) 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 bar, 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.
KW - Apoptosis
KW - Necrosis
KW - Nitric oxide
KW - Peroxynitrite
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U2 - 10.1016/S1382-6689(98)00016-7
DO - 10.1016/S1382-6689(98)00016-7
M3 - Article
C2 - 21781879
AN - SCOPUS:0031851572
SN - 1382-6689
VL - 6
SP - 35
EP - 44
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
IS - 1
ER -