Effects of aldehyde-modified proteins on mesangial cell-matrix interaction.
We examined the effect of aldehyde-modified matrix macromolecules on mesangial cell function in vitro, using incubated rat glomerular mesangial cells. Laminin and fibronectin were modified by incubation for 24 h with 50 mM glycolaldehyde (GA), a highly reactive cross-linking glycation product, with or without equimolar aminoguanidine. GA-modified laminin and fibronectin caused marked inhibition of cell adhesion. Cell spreading was reduced on the GA-modified laminin. In contrast, the GA-modified fibronectin had no effect on cell spreading. The study of thymidine incorporation by mesangial cells showed that the GA-modified fibronectin had a diminished mitogenic activity against cells. The content of advanced glycation end-product (AGE), which was determined by fluorescence at 370 nm excitation and 440 nm emission wavelength, increased and intermolecular cross-links appeared in the GA-modified proteins. To a large extent, aminoguanidine restored the structural alterations and functional deteriorations described above. We conclude that GA-modified matrix proteins diminish their functional properties against mesangial cells and affect cellular functions.
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
G
G
Hasegawa
K
K
Nakano
Y
Y
Tsutsumi
M
M
Kondo
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017127:Glycation End Products, Advanced; D006146:Guanidines / Q000494:pharmacology*; D007797:Laminin / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000378:metabolism
D005353:Fibronectins; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007797:Laminin; D000079:Acetaldehyde; C004479:pimagedine; D013936:Thymidine; C010972:glycolaldehyde