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Extracellular signal-regulated kinases 1 and 2 activation in endothelial cells exposed to cyclic strainThe aim of this study was to determine whether extracellular signal-regulated kinases 1/2 (ERK1/ERK2) are activated and might play a role in enhanced proliferation and morphological change induced by strain. Bovine aortic endothelial cells (BAEC) were subjected to an average of 6 or 10% strain at a rate of 60 cycles/min for up to 4 h. Cyclic strain caused strain- and time-dependent phosphorylation and activation of ERK1/ERK2. Peak phosphorylation and activation of ERK1/ERK2 induced by 10% strain were at 10 min. A specific ERK1/ERK2 kinase inhibitor, PD-98059, inhibited phosphorylation and activation of ERK1/ERK2 but did not inhibit the increased cell proliferation and cell alignment induced by strain. Treatment of BAEC with 2,5-di-tert-butyl-1, 4-benzohydroquinone, to deplete inositol trisphosphate-sensitive calcium storage, and gadolinium chloride, a Ca2+ channel blocker, did not inhibit the activation of ERK1/ERK2. Strain-induced ERK1/ERK2 activation was partly inhibited by the protein kinase C inhibitor calphostin C and completely inhibited by the tyrosine kinase inhibitor genistein. These data suggest that 1) ERK1/ERK2 are not critically involved in the strain-induced cell proliferation and orientation, 2) strain-dependent activation of ERK1/ERK2 is independent of intracellular and extracellular calcium mobilization, and 3) protein kinase C activation and tyrosine kinase regulate strain-induced activation of ERK1/ERK2.
Document ID
20040142088
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Ikeda, M.
(Yale University School of Medicine New Haven, Connecticut 06510, United States)
Takei, T.
Mills, I.
Kito, H.
Sumpio, B. E.
Date Acquired
August 22, 2013
Publication Date
February 1, 1999
Publication Information
Publication: The American journal of physiology
Volume: 276
Issue: 2 Pt 2
ISSN: 0002-9513
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: R01-HL-47345
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cell Biology
Non-NASA Center

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