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

Entong Wang, Yili Yin, Min Zhao, John V. Forrester, Colin D. 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 microM), had no effect on this response. Rather, EF responses were mediated via decreased entry of cells into S phase from G1 phase, as shown by flow cytometry. Western blot showed that EFs decreased G1-specific cyclin E expression and increased cyclin/cyclin-dependent kinase complex inhibitor p27kipl expression. Thus EFs controlled VEC proliferation through induction of cell cycle arrest at G1 by down-regulation of cyclin E expression and up-regulation of p27kipl 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 (US)
Pages (from-to)458-460
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number3
StatePublished - 2003
Externally publishedYes

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G1 Phase Cell Cycle Checkpoints
Endothelial cells
Cell proliferation
Endothelial Cells
Cells
Electric fields
Cell Proliferation
Cyclin E
Apoptosis
Cyclins
Caspase Inhibitors
Cyclin-Dependent Kinases
Vascular Endothelium
G1 Phase
Cell Cycle Checkpoints
S Phase
Mitosis
Flow Cytometry
Up-Regulation
Down-Regulation

Cite this

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

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 17, No. 3, 2003, p. 458-460.

Research output: Contribution to journalArticle

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