Nitric oxide protects murine embryonic liver cells (BNL CL.2) from cytotoxicity induced by glucose deprivation.
We investigated the protective effects of nitric oxide on cell death of murine embryonic liver cells (BNL CL.2) after glucose deprivation. Endogenous nitric oxide production by BNL CL.2 cells was induced by 6 hr pretreatment with interferon-gamma and lipopolysaccharide. We used sodium nitroprusside and S-nitroso-L-glutathione as exogenous nitric oxide-generating compounds. All agents were used at doses that did not show direct cytotoxicity as measured by crystal violet staining assay. In the BNL CL.2 cells, the viability dropped very steeply after 24 hr incubation with glucose-free media. Endogenous nitric oxide produced by treatment of the cells with interferon-gamma and lipopolysaccharide protected the cells from glucose deprivation-induced cytotoxicity, but did not protect them in the presence of the nitric oxide synthesis inhibitor, N(G)-monomethyl-L-arginine. Exogenous nitric oxide protected the cells from glucose deprivation-induced cytotoxicity in a concentration-dependent manner. Cytoprotection by nitric oxide donors was abolished by the use of nitric oxide scavenger, 2-phenyl-4,4,5,5,-tetramethylimidazole, but not by the soluble guanosine cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. In addition, cytoprotective effects comparable to endogenous or exogenous nitric oxide were not observed when the cells were incubated with dibutyl guanosine 3',5'-cyclic monophosphate. Based upon these results, we suggest that nitric oxide may enhance the cell survival of BNL CL.2 cells after glucose deprivation via a guanosine 3',5'-cyclic monophosphate-independent pathway.
Pae
H O
HO
Department of Microbiology and Immunology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang University, Iksan, Chonbug, Korea.
Kim
H G
HG
Paik
Y S
YS
Paik
S G
SG
Kim
Y M
YM
Oh
G S
GS
Chung
H T
HT
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004926:Escherichia coli; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D026422:S-Nitrosoglutathione
D003497:Cyclic N-Oxides; D007093:Imidazoles; D008070:Lipopolysaccharides; D009603:Nitroso Compounds; D009599:Nitroprusside; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D026422:S-Nitrosoglutathione; D007371:Interferon-gamma; D005978:Glutathione; D005947:Glucose; D000111:Acetylcysteine