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Physiological electric fields control the G 1 /S phase cell cycle checkpoint to inhibit endothelial cell proliferation
Author(s) -
Wang Entong,
Yin Yili,
Zhao Min,
Forrester John V.,
McCaig Colin D.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0510fje
Subject(s) - cell cycle , cell growth , microbiology and biotechnology , apoptosis , cyclin a , cyclin , angiogenesis , cell cycle checkpoint , flow cytometry , biology , cyclin b1 , cyclin e , chemistry , cyclin dependent kinase 1 , cancer research , biochemistry
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 μM), 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.