Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation

Entong Wang, Y. Yin, Min Zhao, John Vincent Forrester, Colin Darnley McCaig

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Vascular endothelial cell (VEC) proliferation is a key event in angiogenesis and is tightly regulated. Electric potential differences exist around the vascular endothelium and give rise to endogenous electric fields (EFs), whether these EFs influence VEC proliferation is unclear. We exposed cultured VECs to applied EFs of physiological strengths for up to 72 h. EF at 50 or 100 mV/mm did not influence cell proliferation, but at 200 mV/mm, cell density, cell growth rate, and mitosis index decreased significantly. EF-induced reduction in VEC proliferation was not due to increased apoptosis, because caspase apoptosis inhibitor Z-VAD-FMK (20 muM), had no effect on this response. Rather, EF responses were mediated via decreased entry of cells into S phase from G(1) phase, as shown by flow cytometry. Western blot showed that EFs decreased G(1)-specific cyclin E expression and increased cyclin/cyclin-dependent kinase complex inhibitor p27(kip1) expression. Thus EFs controlled VEC proliferation through induction of cell cycle arrest at G(1) by down-regulation of cyclin E expression and up-regulation of p27(kip1) expression, rather than by promoting apoptosis. If control of the cell cycle by endogenous EFs extends beyond VECs, this would be of widespread biological significance in vivo.

Original languageEnglish
Pages (from-to)458-460
Number of pages2
JournalThe FASEB Journal
Volume17
Issue number3
DOIs
Publication statusPublished - 2003

Keywords

  • bioelectricity
  • cell growth
  • cyclin
  • apoptosis
  • RHEUMATOID-ARTHRITIS
  • THERAPEUTIC ANGIOGENESIS
  • GROWTH
  • INVITRO
  • CANCER
  • NEOVASCULARIZATION
  • MECHANISMS
  • REGULATORS
  • APOPTOSIS
  • RELEASE

Cite this

Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation. / Wang, Entong; Yin, Y.; Zhao, Min; Forrester, John Vincent; McCaig, Colin Darnley.

In: The FASEB Journal, Vol. 17, No. 3, 2003, p. 458-460.

Research output: Contribution to journalArticle

Wang, Entong ; Yin, Y. ; Zhao, Min ; Forrester, John Vincent ; McCaig, Colin Darnley. / Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation. In: The FASEB Journal. 2003 ; Vol. 17, No. 3. pp. 458-460.
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