Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qin, X.
Right arrow Articles by Halperin, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qin, X.
Right arrow Articles by Halperin, J. A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:2653-2661, 2004
© 2004 by the American Diabetes Association, Inc.

Glycation Inactivation of the Complement Regulatory Protein CD59

A Possible Role in the Pathogenesis of the Vascular Complications of Human Diabetes

Xuebin Qin1,2, Allison Goldfine3, Nicole Krumrei2, Luciano Grubissich2, Juan Acosta2,4, Michael Chorev2, Arthur P. Hays5, and Jose A. Halperin1,2

1 Hematology Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
2 Laboratory for Translational Research, Harvard Medical School, Boston, Massachusetts
3 Joslin Diabetes Center, Boston, Massachusetts
4 Beth Israel Deaconess Medical Center, Boston, Massachusetts
5 Columbia University, New York, New York

Micro- and macrovascular diseases are major causes of morbidity and mortality in the diabetic population, but the cellular and molecular mechanisms that link hyperglycemia to these complications remain incompletely understood. We proposed that in human diabetes, inhibition by glycation of the complement regulatory protein CD59 increases deposition of the membrane attack complex (MAC) of complement, contributing to the higher vascular risk. We report here 1) the generation and characterization of an anti–glycated human CD59 (hCD59) specific antibody, 2) the detection with this antibody of glycated hCD59 colocalized with MAC in kidneys and nerves from diabetic but not from nondiabetic subjects, and 3) a significantly reduced activity of hCD59 in erythrocytes from diabetic subjects, a finding consistent with glycation inactivation of hCD59 in vivo. Because hCD59 acts as a specific inhibitor of MAC formation, these findings provide a molecular explanation for the increased MAC deposition reportedly found in the target organs of diabetic complications. We conclude that glycation inactivation of hCD59 that leads to increased MAC deposition may contribute to the extensive vascular pathology that complicates human diabetes.

Address correspondence and reprint requests to Dr. Jose A. Halperin, Harvard Medical School, 1 Kendall Square, Building 600, 3rd Floor, Cambridge, MA 02139. E-mail: jose_halperin{at}hms.harvard.edu


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Arch Intern MedHome page
T. K. Hansen, M.-A. Gall, L. Tarnow, S. Thiel, C. D. Stehouwer, C. G. Schalkwijk, H.-H. Parving, and A. Flyvbjerg
Mannose-binding lectin and mortality in type 2 diabetes.
Arch Intern Med, October 9, 2006; 166(18): 2007 - 2013.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
S. P. Berger, A. Roos, and M. R. Daha
Complement and the kidney: What the nephrologist needs to know in 2006?
Nephrol. Dial. Transplant., December 1, 2005; 20(12): 2613 - 2619.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Huang, C. A. Smith, H. Song, B. P. Morgan, R. Abagyan, and S. Tomlinson
Insights into the Human CD59 Complement Binding Interface Toward Engineering New Therapeutics
J. Biol. Chem., October 7, 2005; 280(40): 34073 - 34079.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.