Inhibitory and enhancing effects of NO on H(2)O(2) toxicity: dependence on the concentrations of NO and H(2)O(2).
Nitric oxide (NO) has been shown to both enhance hydrogen peroxide (H(2)O(2)) toxicity and protect cells against H(2)O(2) toxicity. In order to resolve this apparent contradiction, we here studied the effects of NO on H(2)O(2) toxicity in cultured liver endothelial cells over a wide range of NO and H(2)O(2) concentrations. NO was generated by spermine NONOate (SpNO, 0.001-1 mM), H(2)O(2) was generated continuously by glucose/glucose oxidase (GOD, 20-300 U/l), or added as a bolus (200 microM). SpNO concentrations between 0.01 and 0.1 mM provided protection against H(2)O(2)-induced cell death. SpNO concentrations >0.1 mM were injurious with low H(2)O(2) concentrations, but protective at high H(2)O(2) concentrations. Protection appeared to be mainly due to inhibition of lipid peroxidation, for which SpNO concentrations as low as 0.01 mM were sufficient. SpNO in high concentration (1 mM) consistently raised H(2)O(2) steady-state levels in line with inhibition of H(2)O(2) degradation. Thus, the overall effect of NO on H(2)O(2) toxicity can be switched within the same cellular model, with protection being predominant at low NO and high H(2)O(2) levels and enhancement being predominant with high NO and low H(2)O(2) levels.
Rauen
Ursula
U
Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstr. 55, Essen 45122, Germany. ursula.rauen@uni-duisburg-essen.de
Li
Tongju
T
de Groot
Herbert
H
D000818:Animals; D017209:Apoptosis; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005949:Glucose Oxidase; D006152:Cyclic GMP