Is ceruloplasmin an important catalyst for S-nitrosothiol generation in hypercholesterolemia?

Nitric oxide ((NO)-N-.) reacts with thiol-containing biomolecules to form S -nitrosothiols (RSNOs). RSNOs are considered as (NO)-N-. reservoirs as they generate (NO)-N-. by homolytic cleavage. Ceruloplasmin has recently been s uggested to have a potent catalytic activity towards RSNO production. Consi dering that (NO)-N-. activity is impaired in hypercholesterolemia and that RSNOs may act as important (NO)-N-. donors, we investigated the relation be tween concentrations of ceruloplasmin and RSNOs in plasma of hypercholester olemic (HC) patients compared to normolipidemic (N) controls. Concentration s of ceruloplasmin (0.36 +/- 0.07 x 0.49 +/- 0.11 mg/dl, N x HC), nitrate ( 19.10 +/- 12.03 x 40.19 +/- 18.70 muM, N x HC), RSNOs (0.25 +/- 0.20 x 0.53 +/- 0.26 muM, N x HC), nitrated LDL (19.51 +/- 6.98 x 35.29 +/- 17.57 nM n itro-BSA equivalents, N x HC), and cholesteryl eater-derived hydroxy/hydrop eroxides (CEOOH, 0.19 +/- 0.06 x 1.46 +/- 0.97 muM) were increased in plasm a of HC as compared to N. No difference was found for nitrite levels betwee n the two groups (1.01 +/- 053 x 1.02 +/- 0.33 muM, N x HC). The concentrat ions of RSNOs, nitrate, and nitrated LDL were positively correlated to thos e of total cholesterol, LDL cholesterol, and apoB. Ceruloplasmin levels wer e directly correlated to apoB and apoE concentrations. Data suggest that: ( i) ceruloplasmin may have a role in the enhancement of RSNOs found in hyper cholesterolemia; (ii) the lower (NO)-N-. bioactivity associated with hyperc holesterolemia is not related to a RSNOs paucity or a defective (NO)-N-. re lease from RSNOs; and (iii) the increased nitrotyrosine levels found in hyp ercholesterolemia indicate that superoxide radicals contribute to inactivat ion of (NO)-N-., directly generated by (NO)-N-. synthase or originated by R SNO decomposition. (C) 2001 Elsevier Science Inc.