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Pro-survival effect of Dock180 overexpression on rat-derived H9C2 cardiomyocytes

Med Sci Monit Basic Res. 2013 Jan 14:19:12-9. doi: 10.12659/msmbr.883738.

Abstract

Background: Integrin รข1 subunit and its downstream molecule, focal adhesion kinase (FAK), have been demonstrated to be indispensible to the promotion of cell proliferation and survival and anti-apoptosis in cardiomyocytes via activation of their downstream pro-survival signaling molecule, AKT. As a component of the integrin pathway, Dock180 (dedicator of cytokinesis 1) protein is also thought to be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes.

Material/methods: Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hDock180, a human Dock180 overexpression eukaryotic recombinant plasmid. The rat and human Dock180 mRNA and protein expression, apoptosis and cell proliferation and survival were analyzed in the H9C2 cardiomyocytes treated with either hypoxia/reoxygenation (H/R) or not, respectively.

Results: Human Dock180 mRNA overexpression could significantly increase the Dock180 protein expression in the H9C2 cardiomyocytes, no matter whether treated with H/R or not. Dock180 overexpression could promote the cell proliferation and survival and anti-apoptosis, and relieve the cell proliferative and survival inhibition and apoptosis induced by H/R in the H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule AKT.

Conclusions: Dock180 could act as a pro-survival molecule in H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule, AKT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis / genetics
  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • Cytoskeleton / metabolism
  • Humans
  • Integrins / metabolism
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Actins
  • DOCK1 protein, human
  • DOCK180 protein, rat
  • Integrins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • rac GTP-Binding Proteins