The Src/PLC/PKC/MEK/ERK signaling pathway is involved in aortic smooth muscle cell proliferation induced by glycated LDL

Hyun Mi Cho, Sung Hee Choi, Ki Chul Hwang, Sue Young Oh, Ho Gyung Kim, Deok Hyo Yoon, Myung Ae Choi, So Yeon Lim, Heesang Song, Yangsoo Jang, Tae Woong Kim

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29 Citations (Scopus)

Abstract

Low density lipoproteins (LDL) play important roles in the pathogenesis of atherosclerosis. Diabetes is associated with accelerated atherosclerosis leading to cardiovascular disease in diabetic patients. Although LDL stimulates the proliferation of arterial smooth muscle cells (SMC), the mechanisms are not fully understood. We examined the effects of native LDL and glycated LDL on the extracellular signal-regulated kinase (ERK) pathway. Addition of native and glycated LDL to rat aorta SMCs (RASMCs) stimulated ERK phosphorylation. ERK phosphorylation was not affected by exposure to the Ca2+ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 (5 μM) and inhibition of phospholipase C (PLC) with U73122/U73343 (5 μM) all reduced ERK phosphorylation in response to glycated LDL. In addition, pretreatment of the RASMCs with a cell-permeable mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059, 5 μM) markedly decreased ERK phosphorylation in response to native and glycated LDL. These findings indicate that ERK phosphorylation in response to glycated LDL involves the activation of PKC, PLC, and MEK, but is independent of intracellular Ca2+.

Original languageEnglish
Pages (from-to)60-66
Number of pages7
JournalMolecules and Cells
Volume19
Issue number1
Publication statusPublished - 2005 Dec 1

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Cho, H. M., Choi, S. H., Hwang, K. C., Oh, S. Y., Kim, H. G., Yoon, D. H., Choi, M. A., Lim, S. Y., Song, H., Jang, Y., & Kim, T. W. (2005). The Src/PLC/PKC/MEK/ERK signaling pathway is involved in aortic smooth muscle cell proliferation induced by glycated LDL. Molecules and Cells, 19(1), 60-66.