Involvement of TRPM7 in Cell Growth as a Spontaneously Activated Ca2+ Entry Pathway in Human Retinoblastoma Cells

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概要

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• We investigated the possible involvement of the melastatin family protein TRPM7 in Ca2+-mediated proliferative control of human retinoblastoma (RB) cells. The growth of RB cell was facilitated by elevating the extracellular Ca2+ concentration with a parallel increase in the magnitude of spontaneous Ca2+ influx. Under nystatin-perforated voltage-clamp, RB cells exhibited an outward-rectifying, spontaneous cation current (Ispont) having Ca2+/Mg2+-inhibited but -permeating properties. Various cation channel blockers inhibiting Ispont (Gd3+, La3+, LOE908, 2-APB) suppressed the spontaneous Ca2+ influx and decelerated the growth of RB cells with similar efficacies. Excision of the RB cell membrane (inside-out) into MgATP-free solution induced a 70pS single channel activity, which was effectively inhibited by millimolar concentrations of Mg2+ or MgATP. RT-PCR and immunocytochemical experiments revealed the expression of TRPM7 mRNA and protein in RB cells, and heterologous expression of TRPM7 in HEK293 cells reproduced the key features of Ispont. In contrast, elimination of this protein from RB cells by siRNA silencing markedly reduced Ispont density and the magnitude of spontaneous Ca2+ influx, which was paralleled by decreased TRPM7 immunoreactivity, decelerated cell proliferation, and retarded G1/S cell cycle progression. These results suggest a significant regulatory role of TRPM7 for RB cell proliferation as a spontaneously activated Ca2+ influx pathway.

• 公益社団法人 日本薬理学会の論文

著者

• MORITA Hiromitsu

  Department of Pharmacology, College of Medicine, University of Vermont

• HARA Yuji

  Laboratory of Molecular Biology, Graduate School of Engineering, Kyoto University

• Inoue Ryuji

  Department Of Pharmacology Faculty Of Medicine Kyushu University

• Sumimoto Hideki

  Medical Institute Of Bioregulation Kyushu University

• Ito Yushi

  Department Of Neonatology National Center For Child Health And Development

• HANANO Toyohisa

  Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University

• SHI Juan

  Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University

• Mori Emiko

  Laboratory Of Molecular Biology Department Of Synthetic Chemistry And Biological Chemistry Graduate

• Shi Juan

  Department Of Anatomy The Fourth Military Medical University

• Umebayashi Chisato

  Department Of Pharmacology Graduate School Of Medical Sciences Kyushu University

• Mori Yasuo

  Laboratory Of Food Chemistry Faculty Of Fisheries Kagoshima University

• Morita Hiromitsu

  Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University

• Inoue Ryuji

  Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University

• Ito Yushi

  Department of Health Science, Kumamoto Health Science University

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