ERK mediates effects of glycated albumin in mesangial cells.
The alterations in glomerular cell biology induced by glycated albumin resemble those caused by high ambient glucose, but are operative in physiologic (5.5 mM) glucose concentration. Recently, high glucose has been shown to activate extracellular signal-related kinase (ERK) in mesangial cells, but whether the mitogen-activated protein kinase (MAPK) cascade participates in signal transduction triggered by glycated albumin is unknown. Using a specific inhibitor of MAPK/ERK kinase, we demonstrate for the first time that activation of ERK is required for the inhibition of cell growth and enhanced elaboration of extracellular matrix protein provoked by glycated albumin. These findings indicate that the MAPK/ERK pathway mediates biologic activities of this glycated protein.
Cohen
M P
MP
Institute of Metabolic Research and Exocell, Inc., University City Science Center, Philadelphia, Pennsylvania, 19104, USA.
Shea
E
E
Shearman
C W
CW
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction; D000093423:Glycated Serum Albumin
D004791:Enzyme Inhibitors; D005353:Fibronectins; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000093423:Glycated Serum Albumin