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Is ceruloplasmin an important catalyst for S-nitrosothiol generation in hypercholesterolemia?
作者姓名:Moriel P  Pereira IR  Bertolami MC  Abdalla DS
摘    要:

收稿时间:4 May 2000

Is ceruloplasmin an important catalyst for S-nitrosothiol generation in hypercholesterolemia?
Moriel P,Pereira IR,Bertolami MC,Abdalla DS.Is ceruloplasmin an important catalyst for S-nitrosothiol generation in hypercholesterolemia?[J].Free Radical Biology & Medicine,2001,30(3):318-326.
Authors:Moriel P  Pereira I R  Bertolami M C  Abdalla D S
Institution:1. Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil;2. Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil;1. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China;2. State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China;1. Department of Chemistry, Faculty of Arts and Sciences, Sakarya University, Sakarya, Turkey;2. Gebze Technical University, Department of Chemistry, Faculty of Basic Sciences, P.K. 141, 41400 Gebze, Kocaeli, Turkey;1. State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China;2. School of Chemistry and Chemical Engineering, Center for Atomic Engineering of Advanced Materials, and Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, Anhui University, Hefei, Anhui, 230601, China;3. School of Chemistry and Molecular Engineering, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China
Abstract: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.
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