title: Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation.
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.
authors.affiliation: Department of Biomedical Sciences, Institute of Medical Sciences, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Entong
authors.initials: E
authors.lastname: Wang
authors.forename: Yili
authors.initials: Y
authors.lastname: Yin
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.forename: Colin D
authors.initials: CD
authors.lastname: McCaig
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004560:Electricity; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase; D008954:Models, Biological; D016196:S Phase
chemical_list: D018797:Cell Cycle Proteins