NASA Logo

NTRS

NTRS - NASA Technical Reports Server

Back to Results
Ceruloplasmin and cardiovascular diseaseTransition metal ion-mediated oxidation is a commonly used model system for studies of the chemical, structural, and functional modifications of low-density lipoprotein (LDL). The physiological relevance of studies using free metal ions is unclear and has led to an exploration of free metal ion-independent mechanisms of oxidation. We and others have investigated the role of human ceruloplasmin (Cp) in oxidative processes because it the principal copper-containing protein in serum. There is an abundance of epidemiological data that suggests that serum Cp may be an important risk factor predicting myocardial infarction and cardiovascular disease. Biochemical studies have shown that Cp is a potent catalyst of LDL oxidation in vitro. The pro-oxidant activity of Cp requires an intact structure, and a single copper atom at the surface of the protein, near His(426), is required for LDL oxidation. Under conditions where inhibitory protein (such as albumin) is present, LDL oxidation by Cp is optimal in the presence of superoxide, which reduces the surface copper atom of Cp. Cultured vascular endothelial and smooth muscle cells also oxidize LDL in the presence of Cp. Superoxide release by these cells is a critical factor regulating the rate of oxidation. Cultured monocytic cells, when activated by zymosan, can oxidize LDL, but these cells are unique in their secretion of Cp. Inhibitor studies using Cp-specific antibodies and antisense oligonucleotides show that Cp is a major contributor to LDL oxidation by these cells. The role of Cp in lipoprotein oxidation and atherosclerotic lesion progression in vivo has not been directly assessed and is an important area for future studies.
Document ID
20040141442
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Fox, P. L.
(The Lerner Research Institute, Cleveland Clinic Foundation Cleveland, OH 44195, United States)
Mazumder, B.
Ehrenwald, E.
Mukhopadhyay, C. K.
Date Acquired
August 22, 2013
Publication Date
June 15, 2000
Publication Information
Publication: Free radical biology & medicine
Volume: 28
Issue: 12
ISSN: 0891-5849
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL29582
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cell Biology
Review
Non-NASA Center
Review, Tutorial

Available Downloads

There are no available downloads for this record.
No Preview Available