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Heat‐shock protein 27 is a major methylglyoxal‐modified protein in endothelial cells
Author(s) -
Schalkwijk Casper G.,
van Bezu Jan,
van der Schors Roel C.,
Uchida Koji,
Stehouwer Coen D.A.,
van Hinsbergh Victor W.M.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.086
Subject(s) - methylglyoxal , troglitazone , chemistry , biochemistry , lysine , glycation , heat shock protein , endothelial stem cell , glyoxal , arginine , intracellular , medicine , amino acid , enzyme , in vitro , peroxisome proliferator activated receptor , receptor , organic chemistry , gene
In endothelial cells cultured under high glucose conditions, methylglyoxal is the major intracellular precursor in the formation of advanced glycation endproducts. We found that endothelial cells incubated with 30 mM d ‐glucose produced approximately 2‐fold higher levels of methylglyoxal but not 3‐deoxyglucosone and glyoxal, as compared to 5 mM d ‐glucose. Under hyperglycaemic conditions, the methylglyoxal‐arginine adduct argpyrimidine as detected with a specific antibody, but not N e ‐(carboxymethyl)lysine and N e ‐(carboxyethyl)lysine, was significantly elevated. The glyoxylase I inhibitor HCCG and the PPARγ ligand troglitazone also increased argpyrimidine levels. Increased levels of argpyrimidine by glucose, HCCG and troglitazone are accompanied by a decrease in proliferation of endothelial cells. A 27 kDa protein was detected as a major argpyrimidine‐modified protein. With in‐gel digestion and mass spectrometric analysis, we identified this major protein as heat‐shock protein 27 (Hsp27). This argpyrimidine modification of Hsp27 may contribute to changes in endothelial cell function associated to diabetes.