Big Mitogen-Activated Protein Kinase 1 Protects Cultured Rat Aortic Smooth Muscle Cells From Oxidative Damage

• Zhao Jing

  Department of Pharmacology, Nara Medical University School of Medicine, Japan

• Kyotani Yoji

  Department of Pharmacology, Nara Medical University School of Medicine, Japan

• Itoh Satoyasu

  Department of Pharmacology, Nara Medical University School of Medicine, Japan

• Nakayama Hitoshi

  Department of Pharmacology, Nara Medical University School of Medicine, Japan

• Isosaki Minoru

  Department of Pharmacology, Nara Medical University School of Medicine, Japan

• Yoshizumi Masanori

  Department of Pharmacology, Nara Medical University School of Medicine, Japan

Abstract

Oxidative stress is considered a major mediator of arteriosclerosis. In vascular smooth muscle cells, oxidative stress–induced cell death (including apoptosis) is probably related to arterial calcification in arteriosclerosis. Big mitogen-activated protein kinase-1 / extracellular signal–regulated kinase 5 (BMK1/ERK5) is a newly identified member of the mitogen-activated protein kinases family. Like Src tyrosine kinase, BMK1/ERK5 is known to be sensitive to oxidative stress; however, its pathophysiological significance is poorly understood. In this study, we investigated the involvement of BMK1 and Src in H₂O₂-induced cell death using cultured rat aortic smooth muscle cells (RASMCs). Cell apoptosis was evaluated by using the TdT-mediated dUTP nick end labeling (TUNEL) method, and BMK1 and Src activities were determined by Western blotting. The main results are as follows: 1) BMK1 and Src were activated by H₂O₂ in a time- and concentration-dependent manner in RASMCs; 2) BMK1 activation by H₂O₂ was attenuated both in Src-knockdown RASMCs and in RASMCs pretreated with 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a Src family kinases inhibitor; and 3) H₂O₂-induced cell death was increased in BMK1- and Src-knockdown RASMCs as well as in PP2-treated RASMCs. These findings suggested that Src and BMK1 may play defensive and resistive roles against oxidative stress–induced death in RASMCs.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 116 (2), 173-180, 2011

  The Japanese Pharmacological Society

Keywords

• arteriosclerosis
• smooth muscle cell
• big mitogen-activated protein kinase-1 (BMK1)
• calcification
• oxidative stress

Details

• CRID: 1390001205181499520
• NII Article ID: 10029894630
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.11015fp
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 11122054
• Web Site: http://id.ndl.go.jp/bib/11122054
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11122054
• Web Site: https://search.jamas.or.jp/link/ui/2012122852
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed