Advanced glycation end products increase transglutaminase activity in primary porcine tenocytes. J Investig Med 2009 Feb;57(2):460-6
Date
01/08/2009Pubmed ID
19127169Pubmed Central ID
PMC6240446DOI
10.2310/JIM.0b013e3181954ac6Scopus ID
2-s2.0-85047684563 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
OBJECTIVES: Tendon abnormalities, such as increased stiffness, thickness, and excess calcification, occur commonly in patients with diabetes mellitus and cause considerable disability. These changes are frequently attributed to increased cross-linking of extracellular matrix components by advanced glycation end-products (AGEs). However, cellular effects of AGEs, such as increased activity of the cross-linking transglutaminase (Tgase) enzymes, could also contribute to altered tissue biomechanics and calcification in diabetic tendons. We determined the effect of AGE-modified protein on tenocyte Tgase activity.
RESEARCH DESIGN AND METHODS: Primary porcine tenocytes were exposed to N- carboxymethyl-lysine (CML)-modified type I collagen in high or normal glucose media. Protein and mRNA levels of the Tgase enzymes and Tgase activity levels were measured, as were markers of apoptosis. We also determined the effect of antioxidants on CML-collagen mediated Tgase activity.
RESULTS: Carboxymethyl-lysine-collagen increased Tgase activity in tenocytes 2.3- to 5.6-fold over unmodified collagen controls in both normal and high glucose media, without altering enzyme protein levels. Anti-oxidant treatment reduced the effect of CML-collagen on Tgase activity. Deoxyribonucleic acid laddering and annexin V protein levels were not altered by CML-collagen exposure.
CONCLUSIONS: Carboxymethyl-lysine-collagen increased Tgase activity in tenocytes, likely posttranslationally. Increased levels of Tgase-mediated cross-links may contribute to the excess calcification and biomechanical pathology seen in diabetic tendons.
Author List
Rosenthal AK, Gohr CM, Mitton E, Monnier V, Burner TAuthors
Todd W. Burner MD Assistant Professor in the Medicine department at Medical College of WisconsinAnn K. Rosenthal MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntioxidants
Apoptosis
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Gene Expression Regulation, Enzymologic
Glycation End Products, Advanced
Lysine
RNA, Messenger
Stifle
Swine
Tendons
Tetrazolium Salts
Thiazoles
Transglutaminases
