Document Detail

Oligomerization state-dependent hyperlipidemic effect of angiopoietin-like protein 4.
MedLine Citation:
PMID:  15292369     Owner:  NLM     Status:  MEDLINE    
Angiopoietin-like protein 4 (Angptl4) is the second member of the angiopoietin-like family of proteins previously shown to increase plasma triglyceride (TG) levels in vivo. We recently reported that Angptl4 is a variable-sized oligomer formed by intermolecular disulfide bonds and undergoes regulated proteolytic processing upon secretion. We now show that adenoviral overexpression of Angptl4 potently increases plasma TG levels by a mechanism independent of food intake or hepatic VLDL secretion. We determined that cysteine residues at positions 76 and 80 of Angptl4, conserved among mouse, rat, and human, are required to form higher order structures. By generating adenoviral expression vectors of Angptl4 containing different epitope tags at both N and C termini, we show that loss of oligomerization results in decreased stability of the N-terminal coiled-coil domain of Angptl4 as well as decreased ability to increase plasma TG levels, suggesting that intermolecular disulfide bond formation plays important roles in determining the magnitude of the hyperlipidemic effect of Angptl4. Because Angptl4 is more potent than Angptl3 in increasing plasma TG levels in mice, inappropriate oligomerization of Angptl4 could be associated with disorders of lipid metabolism in vivo.
Hongfei Ge; Guoqing Yang; Xinxin Yu; Tiffany Pourbahrami; Cai Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-08-01
Journal Detail:
Title:  Journal of lipid research     Volume:  45     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-18     Completed Date:  2005-04-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2071-9     Citation Subset:  IM    
Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-8854, USA.
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MeSH Terms
Adenoviridae / genetics
Amino Acid Sequence
Animal Feed
Blood Proteins
Blotting, Northern
Cysteine / chemistry
Disulfides / chemistry
Epitopes / chemistry
Intercellular Signaling Peptides and Proteins / chemistry*,  metabolism
Lipid Metabolism
Lipids / chemistry
Lipoproteins / chemistry
Lipoproteins, VLDL / metabolism
Mice, Inbred C57BL
Mice, Inbred ICR
Molecular Sequence Data
Polyethylene Glycols / pharmacology
Polymerase Chain Reaction
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Time Factors
Triglycerides / blood*
Grant Support
Reg. No./Substance:
0/ANGPTL4 protein, human; 0/Angiopoietins; 0/Angptl4 protein, mouse; 0/Blood Proteins; 0/Disulfides; 0/Epitopes; 0/Intercellular Signaling Peptides and Proteins; 0/Lipids; 0/Lipoproteins; 0/Lipoproteins, VLDL; 0/Polyethylene Glycols; 0/Triglycerides; 25301-02-4/tyloxapol; 52-90-4/Cysteine

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