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Advanced Glycation Endproducts Stimulate Mitogen-Activated Protein Kinase and Proliferation in Rabbit Vascular Smooth Muscle Cells☆

https://doi.org/10.1006/bbrc.1997.7424Get rights and content

Abstract

Advanced glycation end products of bovine serum albumin (AGEs-BSA) exhibited biphasic effects on the proliferation of cultured rabbit vascular smooth muscle cells (VSMCs) in terms of [3H]thymidine incorporation and cell number count; a stimulatory effect was observed at 1-10 μg/ml and an inhibitory effect at more than 20 μg/ml, while it inhibited [3H]thymidine incorporation even at 1-10 μg/ml in cultured bovine vascular endothelial cells (VECs). Transient activation of p42 mitogen-activated protein kinase (MAPK) with a peak at around 5 min and a subsequent sustained phase was induced by AGEs-BSA in VSMCs, but not in VECs. The dependence of MAPK activation on AGEs-BSA dose was correlated with that of VSMCs proliferation.

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AGEs, advanced glycation end productsVECs, vascular endothelial cells; VSMCs, vascular smooth muscle cells; MAPK, mitogen-activated protein kinase; PDGF, platelet-derived growth factor; RAGE, receptor for AGE; DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; BSA, bovine serum albumin; PBS, phosphate-buffered saline; MBP, myelin basic protein; ANOVA, analysis of variance;

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Correspondence address: T.Watanabe, Third Department of Internal Medicine, Fukushima Medical College, Hikarigaoka, 1, Fukushima-City, Fukushima 960-12, Japan. Fax: 81-0245-48-3043.

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