AJP - Renal Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 292: F599-F606, 2007. First published September 12, 2006; doi:10.1152/ajprenal.00303.2006
0363-6127/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/2/F599    most recent
00303.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (8)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, N. X.
Right arrow Articles by Moe, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, N. X.
Right arrow Articles by Moe, S. M.

Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins

Neal X. Chen,1 Kalisha D. O'Neill,1 Xianming Chen,1 Danxia Duan,1 Exing Wang,1 Michael S. Sturek,1 Jason M. Edwards,1 and Sharon M. Moe1,2

1Indiana University School of Medicine, and 2Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana

Submitted 2 August 2006 ; accepted in final form 8 September 2006

Fetuin-A is a known inhibitor of vascular calcification in vitro. In arteries with calcification, there is increased immunostaining for fetuin-A. However, vascular smooth muscle cells (VSMC) do not synthesize fetuin-A, suggesting fetuin-A may be endocytosed to exert its inhibitory effects. To examine the mechanism by which fetuin-A is taken up in bovine VSMC (BVSMC), we examined living cells by confocal microscopy and determined the uptake of Cy5-labeled fetuin-A. The results demonstrated that fetuin-A was taken up in BVSMC only in the presence of extracellular calcium, whereas phosphorus had no effect. Additional studies demonstrated the calcium-dependent uptake was specific for fetuin-A and only observed in BVSMC and osteoblasts, but not epithelial, endothelial, or adipose cells. The uptake was dose dependent, but could not be inhibited by excess unlabeled fetuin-A, suggesting a fluid phase rather than a receptor-mediated process. Fetuin-A also induced a sustained increase in intracellular calcium in BVSMC in the presence of extracellular calcium, whereas there was no increase in the absence of extracellular calcium. To further characterize the uptake, we utilized an inhibitor of annexin calcium channel activity, demonstrating inhibition of both fetuin-A uptake and intracellular calcium increase. Finally, we demonstrate that fetuin-A binds to annexin II at the cell membrane of BVSMC. In summary, our study demonstrates calcium- and annexin-dependent uptake of fetuin-A that leads to a sustained rise in intracellular calcium. This regulated uptake may be a mechanism by which fetuin-A inhibits VSMC calcification in the presence of excess calcium.

annexins; cellular uptake; intracellular calcium; vascular calcification


Address for reprint requests and other correspondence: N. X. Chen, Indiana Univ. School of Medicine, 1001 West 10th St., WD, OPW 526, Indianapolis, IN 46202 (e-mail: xuechen{at}iupui.edu)




This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
M. Mizobuchi, D. Towler, and E. Slatopolsky
Vascular Calcification: The Killer of Patients with Chronic Kidney Disease
J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1453 - 1464.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.