Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

The Src/PLC/PKC/MEK/ERK Signaling Pathway Is Involved in Aortic Smooth Muscle Cell Proliferation induced by Glycated LDL

  • Cho, Hyun-Mi (Department of Biochemistry, Kangwon National University) ;
  • Choi, Sung Hee (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Hwang, Ki-Chul (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Oh, Sue-Young (Department of Biochemistry, Kangwon National University) ;
  • Kim, Ho-Gyung (Department of Biochemistry, Kangwon National University) ;
  • Yoon, Deok-Hyo (Department of Biochemistry, Kangwon National University) ;
  • Choi, Myung-Ae (Department of Biochemistry, Kangwon National University) ;
  • Lim, So Yeon (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Song, Heesang (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Jang, Yangsoo (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Kim, Tae Woong (Department of Biochemistry, Kangwon National University)
  • Received : 2004.08.25
  • Accepted : 2004.09.24
  • Published : 2005.02.28
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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 $Ca^{2+}$ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 ($5{\mu}M$) and inhibition of phospholipase C (PLC) with U73122/U73343 ($5{\mu}M$) 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, $5{\mu}M$) 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 $Ca^{2+}$.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation

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