Protein glycosylation and collagen metabolism in normal and diabetic rats.
The high concentration of glycosylated extracellular proteins found in diabetics may contribute adversely to wound healing. The degree of collagen glycosylation was correlated with collagenase activity and 5-hydroxyproline (5-OHP) levels in surgical wounds of normal and diabetic animals. Expanded polytetrafluoroethylene (PTFE) wound cylinders were implanted subcutaneously in 10 normal and 10 streptozotocin-induced diabetic rats. Nonenzymatic glycosylation (NEG) of protein was inhibited in half the subjects in each group by daily enteral acetylsalicylic acid (ASA). Wound cylinders were removed on the fifth day and assayed for collagenase activity and 5-OHP levels, and the degree of collagen glycosylation was measured with an assay for 5-hydroxymethylfurfural (5-HMF). Results were compared using Student's two-tailed t test. When compared with controls, diabetic animals had less wound 5-OHP (1.87 +/- 0.01 vs 3.11 +/- 0.03 micrograms/cm PTFE) (P less than 0.0001), higher levels of glycosylated collagen (215 +/- 11 vs 150 +/- 9 micrograms 5-HMF/mg protein) (P less than 0.001), and increased collagenase activity (13.5 +/- 0.6 vs 11.7 +/- 0.5 microgram collagen/mg protein/hr) (P less than 0.001). When ASA was added to the diet of diabetic animals, results in each case were statistically indistinguishable from controls. The collagenase activity of nondiabetic animals receiving ASA was decreased from nondiabetic controls (7.6 +/- 0.5 vs 11.7 +/- 0.5 microgram collagen/mg protein/hr) (P less than 0.001). These data show that ASA inhibits NEG of wound collagen in vivo, and ASA may normalize some abnormalities of wound healing found in diabetic animals.
Black
C T
CT
Department of Surgery, University of Texas Medical School, Houston 77030.
Hennessey
P J
PJ
Ford
E G
EG
Andrassy
R J
RJ
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006031:Glycosylation; D003012:Microbial Collagenase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013311:Streptozocin; D014947:Wounds and Injuries / Q000201:enzymology / Q000378:metabolism
D011506:Proteins; D013311:Streptozocin; D003094:Collagen; D003012:Microbial Collagenase