Inhibition of Cu2+-induced LDL oxidation by nitric oxide: a study using donors with different half-time of NO release.
The incubation of low density lipoproteins with Cu++ promotes oxidative modifications that make them atherogenic. Comparable alterations occur in vivo and are modulated by the generation of nitric oxide by endothelial cells or macrophages. Here we report that two donors (NOC-9 and NOC-18) with different half times of NO release (2.7 and >500 min, respectively) inhibit in vitro lipoprotein oxidation promoted by Cu++. Both donors increase the duration of the lag-phase and decrease the maximum rate of conjugated diene formation, prevent the loss of tryptophan in Apo B100, and decrease the formation of fluorescent adducts. The protective effect of NOC-9 was rapidly exhausted and its overall efficacy in preventing LDL oxidation was two orders of magnitude lower than that exhibited by NOC-18. These findings suggest that a continuous flux of NO generation, even at lower concentrations, is more efficient than considerably higher doses released as a burst in protecting both the lipid and the protein moiety of LDL from oxidation.
Seccia
M
M
Department of Medical Sciences, University of Torino, Novara, Italy.
Perugini
C
C
Albano
E
E
Bellomo
G
G
D003300:Copper / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology; D014226:Triazenes / Q000737:chemistry / Q000494:pharmacology
D008077:Lipoproteins, LDL; C093285:NOC 18; D009603:Nitroso Compounds; D014226:Triazenes; C099612:NOC 9; D009569:Nitric Oxide; D003300:Copper