Cellular contraction of collagen lattices is inhibited by nonenzymatic glycation.

Abstract:

:High glucose concentrations associated with diabetes have been shown to cause the nonenzymatic modification of proteins. Reducing sugars covalently bind to free amine groups, undergo Amadori rearrangements, and crosslink with other glucose-modified proteins. Crosslinking of type I collagen by incubation with different concentrations of glucose 6-phosphate for up to 5 days resulted in a nondeformable collagen lattice as assayed by physical compaction analysis. Nonglycated collagen was fully compactible. Fibroblasts cultured on nonglycated collagen lattices were able to contract the lattice over a 5-day period, while fibroblasts on collagen glycated with 50 mM or more glucose 6-phosphate were unable to do this. Cells on both nonglycated and glycated collagen lattices initially lacked organized bundles of actin microfilaments or stress fibers. Over time, the cells on glycated lattices formed stress fibers, suggesting that they were still exerting mechanical force on a nondeformable matrix. These results suggest that crosslinking of collagen fibrils by nonenzymatic glycation alters the physical properties of the extracellular matrix, resulting in changes in the organization of the intracellular actin cytoskeleton.

journal_name

Exp Cell Res

authors

Howard EW,Benton R,Ahern-Moore J,Tomasek JJ

doi

10.1006/excr.1996.0308

subject

Has Abstract

pub_date

1996-10-10 00:00:00

pages

132-7

issue

1

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(96)90308-0

journal_volume

228

pub_type

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