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Record 41 of 642
Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism
External Online Source: doi:10.1074/jbc.271.25.14773
Author and Affiliation:
Mukhopadhyay, C. K.(Cleveland Clinic Research Institute, Department of Cell Biology, Cleveland, Ohio 44195, United States)
Ehrenwald, E.
Fox, P. L.
Abstract: Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.
Publication Date: Jun 21, 1996
Document ID:
20040173187
(Acquired Dec 09, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: The Journal of biological chemistry (ISSN 0021-9258); Volume 271; 25; 14773-8
Publisher Information: United States
Contract/Grant/Task Num: HL29582; HL52692
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: ENDOTHELIUM; FREE RADICALS; INORGANIC PEROXIDES; LIPOPROTEINS; OXIDATION; SMOOTH MUSCLE; AORTA; CATALASE; CATTLE; CULTURED CELLS; DOSAGE; FORMIC ACID; GLUTATHIONE; KINETICS; MANNITOL; OXIDATION-REDUCTION REACTIONS; PHYSIOLOGICAL RESPONSES; THIOUREAS
Other Descriptors: CERULOPLASMIN/PHARMACOLOGY; ENDOTHELIUM, VASCULAR/DRUG EFFECTS/METABOLISM; FREE RADICAL SCAVENGERS/PHARMACOLOGY; LIPOPROTEINS, LDL/DRUG EFFECTS/METABOLISM; MUSCLE, SMOOTH, VASCULAR/DRUG EFFECTS/METABOLISM; SUPEROXIDES/METABOLISM; ANIMALS; AORTA; CATALASE/PHARMACOLOGY; CATTLE; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; FORMIC ACIDS/PHARMACOLOGY; GLUTATHIONE/PHARMACOLOGY; HUMAN; KINETICS; MANNITOL/PHARMACOLOGY; OXIDATION-REDUCTION; SUPEROXIDE DISMUTASE/PHARMACOLOGY; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S; THIOUREA/ANALOGS & DERIVATIVES/PHARMACOLOGY; NASA DISCIPLINE REGULATORY PHYSIOLOGY; NON-NASA CENTER
Availability Source: Other Sources
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