![]()
|
|
||||||||
J. Biol. Chem., Vol. 280, Issue 13, 12310-12315, April 1, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||



||
From the
Institute of Pathology and ||Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44106 and the ¶Institut für Lebensmittelchemie (170), Universität Hohenheim, Garbenstrasse 28, Stuttgart D-70593, Germany
The extracellular matrix in most tissues is characterized by progressive age-related stiffening and loss of proteolytic digestibility that are accelerated in diabetes and can be duplicated by the nonenzymatic reaction of reducing sugars and extracellular matrix proteins. However, most cross-links of the Maillard reaction described so far are present in quantities too low to account for these changes. Here we have determined in human skin and glomerular basement membrane (GBM) collagen the levels of the recently discovered lysine-arginine cross-links derived from glucose, methylglyoxal, glyoxal, and 3-deoxyglucosone, i.e. glucosepane, MODIC, GODIC, and DOGDIC, respectively. Insoluble preparations of skin collagen (n = 110) and glomerular basement membrane (GBM, n = 28) were enzymatically digested, and levels were measured by isotope dilution technique using liquid chromatography/mass spectrometry. In skin, all cross-links increased with age (p < 0.0001) except DOGDIC (p = 0.34). In nondiabetic controls, levels at 90 years were 2000, 30, and 15 pmol/mg for glucosepane, MODIC, and GODIC, respectively. Diabetes, but not renal failure, increased glucosepane to 5000 pmol/mg (p < 0.0001), and for all others, increased it to <60 pmol/mg (p < 0.01). In GBMs, glucosepane reached up to 500 pmol/mg of collagen and was increased in diabetes (p < 0.0001) but not old age. In conclusion, glucosepane is the single major cross-link of the senescent extracellular matrix discovered so far, accounting for up to >120 mole% of triple helical collagen modification in diabetes. Its presence in high quantities may contribute to a number of structural and cell matrix dysfunctions observed in aging and diabetes.
Received for publication, January 20, 2005
* This research was supported by Grants NIA AG18629 and NIDDK DK-57733 from the National Institutes of Health as well as a Mentorship Grant from the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Institute of Pathology, Case Western Reserve University, 2085 Adelbert Rd., Cleveland, OH, 44106. Tel.: 216-368-2930; Fax: 216-368-0495; E-mail: drs7{at}cwru.edu.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
M. E. Craig, A. C. Duffin, P. H. Gallego, A. Lam, J. Cusumano, S. Hing, and K. C Donaghue Plantar Fascia Thickness, a Measure of Tissue Glycation, Predicts the Development of Complications in Adolescents With Type 1 Diabetes Diabetes Care, June 1, 2008; 31(6): 1201 - 1206. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. M. MONNIER, D. R. SELL, Z. DAI, I. NEMET, F. COLLARD, and J. ZHANG The Role of the Amadori Product in the Complications of Diabetes Ann. N.Y. Acad. Sci., April 1, 2008; 1126(1): 81 - 88. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. R. SELL, C. M. STRAUCH, W. SHEN, and V. M. MONNIER Aging, Diabetes, and Renal Failure Catalyze the Oxidation of Lysyl Residues to 2-Aminoadipic Acid in Human Skin Collagen: Evidence for Metal-catalyzed Oxidation Mediated by {alpha}-Dicarbonyls Ann. N.Y. Acad. Sci., April 1, 2008; 1126(1): 205 - 209. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Genuth, W. Sun, P. Cleary, D. R. Sell, W. Dahms, J. Malone, W. Sivitz, V. M. Monnier, and for the DCCT Skin Collagen Ancillary Study Group Glycation and Carboxymethyllysine Levels in Skin Collagen Predict the Risk of Future 10-Year Progression of Diabetic Retinopathy and Nephropathy in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications Participants With Type 1 Diabetes Diabetes, November 1, 2005; 54(11): 3103 - 3111. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |