Lysyl oxidase-mediated crosslinking in granulation tissue collagen in two models of hyperglycemia.
Enzymatically mediated crosslinks and nonenzymatic glycation were quantified in granulation tissue collagen in two models of hyperglycemia, diabetes and galactosemia, that have opposite effects on collagen solubility. The effects of castration, which alters collagen solubility, was also investigated. Collagen from both diabetic and galactosemic rats had significantly increased levels of dihydroxylysinonorleucine (DHLNL), a difunctional reducible crosslink. Galactosemic rats had significantly decreased levels of hydroxypyridinium, a trifunctional product of DHLNL and hydroxylysine, relative to control values, while diabetic rats had normal levels. Values for all other detectable crosslinks in collagen from hyperglycemic rats were indistinguishable from control values. Nonenzymatic glycation was increased in both groups of hyperglycemic rats. In diabetic rats, but not in galactosemic rats, nonenzymatic glycation was strongly correlated with DHLNL content. Castration had no effect on crosslink content of collagen from diabetic or galactosemic rats. This study demonstrates that (1) collagen crosslinking is abnormal in granulation tissue collagen in both experimental diabetes and galactosemia, (2) these changes are similar to those observed in skin collagen from insulin-dependent diabetic subjects and (3) the crosslinking abnormalities are not correlated with alterations in collagen solubility. We conclude that hyperglycemia-associated increases in immature crosslinks cannot account for altered collagen solubility, although impaired maturation of such crosslinks may be partially responsible for the lathyrogenic effect of galactosemia.
Department of Internal Medicine, School of Medicine, University of California, Davis 95616.
K M
KM
Reiser
E C
EC
Crouch
K
K
Chang
J R
JR
Williamson
D000085:Acetates; D019342:Acetic Acid; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D005693:Galactosemias / Q000378:metabolism; D006097:Granulation Tissue / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D000085:Acetates; D001786:Blood Glucose; D004151:Dipeptides; C007428:5,5'-dihydroxylysylnorleucine; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D019342:Acetic Acid