Is ceruloplasmin an important catalyst for S-nitrosothiol generation in hypercholesterolemia?
Nitric oxide (NO) reacts with thiol-containing biomolecules to form S-nitrosothiols (RSNOs). RSNOs are considered as NO reservoirs as they generate NO by homolytic cleavage. Ceruloplasmin has recently been suggested to have a potent catalytic activity towards RSNO production. Considering that NO activity is impaired in hypercholesterolemia and that RSNOs may act as important NO donors, we investigated the relation between concentrations of ceruloplasmin and RSNOs in plasma of hypercholesterolemic (HC) patients compared to normolipidemic (N) controls. Concentrations 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 microM, N x HC), RSNOs (0.25 +/- 0.20 x 0.54 +/- 0.26 microM, N x HC), nitrated LDL (19.51 +/- 6.98 x 35.29 +/- 17.57 nM nitro-BSA equivalents, N x HC), and cholesteryl ester-derived hydroxy/hydroperoxides (CEOOH, 0.19 +/- 0.06 x 1.46 +/- 0.97 microM) were increased in plasma of HC as compared to N. No difference was found for nitrite levels between the two groups (1.01 +/- 0.53 x 1.02 +/- 0.33 microM, N x HC). The concentrations of RSNOs, nitrate, and nitrated LDL were positively correlated to those of total cholesterol, LDL cholesterol, and apoB. Ceruloplasmin levels were directly correlated to apoB and apoE concentrations. Data suggest that: (i) ceruloplasmin may have a role in the enhancement of RSNOs found in hypercholesterolemia; (ii) the lower NO bioactivity associated with hypercholesterolemia is not related to a RSNOs paucity or a defective NO release from RSNOs; and (iii) the increased nitrotyrosine levels found in hypercholesterolemia indicate that superoxide radicals contribute to inactivation of NO, directly generated by NO synthase or originated by RSNO decomposition.
Moriel
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P
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas, Av. Prof. Lineu Prestes, 580, Cidade Universitária-Butantã, 05508-900 São Paulo, Brazil.
Pereira
I R
IR
Bertolami
M C
MC
Abdalla
D S
DS
D001055:Apolipoproteins B / Q000097:blood; D001205:Ascorbic Acid / Q000097:blood; D002384:Catalysis; D002570:Ceruloplasmin / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008623:Mercaptoethanol; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009603:Nitroso Compounds / Q000097:blood*; D026403:S-Nitrosothiols; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood; D014527:Uric Acid / Q000097:blood; D014810:Vitamin E / Q000097:blood
D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D014810:Vitamin E; D014527:Uric Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D002784:Cholesterol; D006861:Hydrogen Peroxide; D002570:Ceruloplasmin; D001205:Ascorbic Acid