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Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 4, pp 711–719 | Cite as

Hypergravity induces ATP release and actin reorganization via tyrosine phosphorylation and RhoA activation in bovine endothelial cells

  • Tetsuya Koyama
  • Chiwaka Kimura
  • Masayuki Hayashi
  • Michi Watanabe
  • Yuji Karashima
  • Masahiro OikeEmail author
Cardiovascular Physiology

Abstract

Mechanical stresses regulate physiological and pathological functions of vascular endothelial cells. We examined, in this study, the effects of hypergravity on endothelial functions. Hypergravity (3 G) applied by low speed centrifuge immediately induced a membrane translocation of small G-protein RhoA and tyrosine phosphorylation of 125 kDa FAK in bovine aortic endothelial cells (BAECs). Hypergravity also induced a transient reorganization of actin fibers in 3 min, which was inhibited by Rho-kinase inhibitor (Y27632) and tyrosine kinase inhibitors (herbimycin A and tyrphostin 46). Furthermore, the extracellular ATP concentration ([ATP]o) was increased by 2 G and 3 G hypergravity in 5 min, and the inhibitors of Rho-kinase, tyrosine kinase, and volume-regulated anion channels (VRAC; verapamil, tamoxifen and fluoxetine) significantly suppressed [ATP]o elevation. Application of 3 G hypergravity for 1 h increased the nuclear uptake of BrdU, which was inhibited by Rho-kinase inhibitor and VARC inhibitors. Furthermore, intermittent application of 3 G hypergravity for 1 or 2 h/day stimulated endothelial migration in 5 days, and this was inhibited by suramin, a P2 antagonist. Collectively, these results indicate that hypergravity induces ATP release and actin reorganization via RhoA activation and FAK phosphorylation, thereby activating cell proliferation and migration in BAECs. These also suggest that gravity can be regarded as an extracorporeal signal that could significantly affect endothelial functions.

Keywords

Endothelial cell Gravity Mechanosensitivity Tyrosine kinase Actin ATP release Cell volume Angiogenesis 

Notes

Acknowledgement

This study was carried out as a part of “Ground Research Announcement for the Space Utilization” promoted by Japan Aerospace Exploration Agency and Japan Space Forum. This study was also supported in part by a grant-in-aid from the Japan Society for the promotion of Science.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Tetsuya Koyama
    • 1
  • Chiwaka Kimura
    • 1
  • Masayuki Hayashi
    • 1
  • Michi Watanabe
    • 1
  • Yuji Karashima
    • 1
  • Masahiro Oike
    • 1
    Email author
  1. 1.Department of Pharmacology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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