CLIC4 channel regulates cell proliferation via changes in intranuclear Clconcentration

• Project/Area Number: 19790168
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MIYAZAKI Hiroaki Kyoto Prefectural University of Medicine, 医学研究科, 助教 (30360027)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 核 / Cl-濃度 / CLIC4 / 細胞増殖 / 細胞周期 / C1^-濃度 / C1濃度

Research Abstract

胃ガン由来細胞株であるMKN28細胞を低Cl-濃度培地で培養を行ったところ、細胞周期のG1期からS期への進行が抑制されることが明らかとなった。また低Cl-処理は、mitogen-activated protein kinase (MAPK)の活性化を誘発することで、細胞周期のG1期からS期の進行を抑制するp21タンパクの発現を亢進することが明らかになった。MAPKを介した転写制御は核内で起こることや、p21などの細胞周期調節タンパク質は細胞の核内で機能していることから、細胞質内のCl-濃度変化が核膜に存在するCl-チャネル(CLIC4)を介し核内のCl-濃度に対しても大きく影響を与え、その結果核内の細胞周期調節タンパクの活性に影響を与えているものと考えられた。

Research Products

• [Journal Article] Regulation of paracellular Na+ and Clconductances by hydrostatic pressure. (2009)
  • Author(s): Tokuda, S., Niisato, N., Nagai, T., Taruno, T., Nakajima, K., Miyazaki, H., Yamada, T., Hosogi, S., Oha, M., Nishio, K., Iwasaki, Y., and Marunaka, Y.
  • Journal Title: Cell Biology International (in press)
  • Peer Reviewed
• [Journal Article] Quercetin stimulates Na+/K+/2Clcotransport via PTK-dependent mechanisms in human airway epithelium. (2009)
  • Author(s): Asano, J., Niisato, N., Nakajima, K., Miyazaki, H., Yasuda, M., Iwasaki, Y., Hama, T., Dejima, K., Hisa, Y., and Marunaka, Y.
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology. (in press)
  • Peer Reviewed
• [Journal Article] Blockers of K+/Cl- transporter/channels diminish proliferation of osteoblastic cells. (2009)
  • Author(s): Maki, M., Miyazaki, H., Niisato, N., Morihara, T., Marunaka, Y., and Kubo, T.
  • Journal Title: Biomedical Research. 30(2) Pages: 137-140
  • NAID: 130004470739
  • Peer Reviewed
• [Journal Article] Blockers of K^+/C1^-transporter/channels diminish proliferation of osteoblastic cells (2009)
  • Author(s): Maki, M
  • Journal Title: Biomedical Research 30 Pages: 137-140
  • Peer Reviewed
• [Journal Article] Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells. (2008)
  • Author(s): Miyazaki, H., Shiozaki, A., Niisato, N., Ohsawa, R., Itoi, H., Ueda, Y., Yamagishi, H., Iwasaki, Y., Nakano, T., Nakahari, T., and Marunaka, Y.
  • Journal Title: Biochemical and Biophysical Research Communications. 366(2) Pages: 506-512
  • Peer Reviewed
• [Journal Article] Chloride ions control the G_1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells. (2008)
  • Author(s): Miyazaki, H.
  • Journal Title: Biochemical and Biophysical Research Communications 366 Pages: 506-512
  • Peer Reviewed
• [Journal Article] 22,Epithelial Na+ channel and ion transport in human nasal polyp and paranasal sinus mucosa. (2007)
  • Author(s): Yasuda, M., Niisato, N., Miyazaki, H., Iwasaki, Y., Hama, T., Dejima, K., Hisa, Y., and Marunaka, Y.
  • Journal Title: Biochemical and Biophysical Research Communications. 362(3) Pages: 753-758
  • Peer Reviewed
• [Journal Article] Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells. (2007)
  • Author(s): Maki, M., Miyazaki, H., Nakajima, K., Yamane, J., Niisato, N., Morihara, T., Kubo, T., and Marunaka, Y.
  • Journal Title: Biochemical and Biophysical Research Communications. 361(4) Pages: 1038-1043
  • Peer Reviewed
• [Journal Article] Essential role of NKCC1 in NGF-induced neurite outgrowth. (2007)
  • Author(s): Nakajima, K., Miyazaki, H., Niisato, N., and Marunaka, Y.
  • Journal Title: Biochemical and Biophysical Research Communications. 359(3) Pages: 604-610
  • Peer Reviewed
• [Journal Article] An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida-induced acute lung injury. (2007)
  • Author(s): Ohsugi, S., Iwasaki, Y., Takemura, Y., Nagata, K., Harada, H., Yokomura, I., Hosogi, S., Yuba, T., Niisato, N., Miyazaki, H., Matsubara, H., Fushiki, S., and Marunaka, Y.
  • Journal Title: Biomedical Research. 28(2) Pages: 91-99
  • NAID: 130004903735
  • Peer Reviewed
• [Journal Article] Abnormal expression of ENaC and SGK1 mRNA induced by dietary sodium in Dahl salt-sensitively hypertensive rats. (2007)
  • Author(s): Aoi, W., Niisato, N., Sawabe, Y., Miyazaki, H., Tokuda, S., Nishio, K., Yoshikawa, T., and Marunaka, Y.
  • Journal Title: Cell Biology International. 31(10) Pages: 1288-1291
  • Peer Reviewed
• [Journal Article] Action of neltenexine on anion secretion in human airway epithelia. (2007)
  • Author(s): Niisato, N., Hasegawa, I., Tokuda, S., Taruno, A., Nakajima, K., Miyazaki, H., Iwasaki, Y., and Marunaka, Y.
  • Journal Title: Biochemical and Biophysical Research Communications. 356(4) Pages: 1050-1055
  • Peer Reviewed
• [Journal Article] Physiological significance of hypotonicityinduced regulatory volume decrease : reduction in intracellular Cl- concentration acting as an intracellular signaling. (2007)
  • Author(s): Miyazaki, H., Shiozaki, A., Niisato, N., and Marunaka, Y.
  • Journal Title: American Journal of Physiology-Renal Physiology. 292(5)
  • Peer Reviewed
• [Journal Article] Physiological significance of hypotonicity-induced regulatory volume decrease:reduction in intracellular CI concentration acting as an intracellular signaling. (2007)
  • Author(s): Miyazaki, H.
  • Journal Title: American Journal of Physiology, Renal Physiology 292 Pages: 1411-1417
  • Peer Reviewed
• [Journal Article] Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells (2007)
  • Author(s): Maki, M.
  • Journal Title: Biochemical and Biophysical Research Communications 361 Pages: 1038-1043
  • Peer Reviewed
• [Presentation] ヒト胃癌細胞株において細胞内crは細胞周期制御シグナルとして作用する (2008)
  • Author(s): 宮崎裕明
  • Organizer: 膜シンポジウム2008
  • Place of Presentation: 大阪大学
  • Year and Date: 2008-11-15
• [Presentation] Intracellular chloride is a key regulator of the G1/S transition in MKN28 human gastric cancer cells (2008)
  • Author(s): Miyazaki, H
  • Organizer: Beatson International Cancer Conference
  • Place of Presentation: Glasgow, Scotland
  • Year and Date: 2008-06-16
• [Presentation] ヒト胃癌細胞株において細胞内CI濃度はG_1/S細胞周期チェックポイントを制御する (2008)
  • Author(s): 宮崎 裕明
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2008-03-27
• [Presentation] 調節性容積減少(RVD)によって引き起こされる細胞内Cl-濃度低下は細胞内シグナルとして機能する (2008)
  • Author(s): 宮崎裕明,新里直美,丸中良典
  • Organizer: 第46回生物物理学会年回
  • Place of Presentation: 福岡
• [Presentation] ヒト胃癌細胞株において細胞内Cl-は細胞周期制御シグナルとして作用する (2008)
  • Author(s): 宮崎裕明,大澤るみ,新里直美,丸中良典
  • Organizer: 膜シンポジウム2008
  • Place of Presentation: 豊中
• [Presentation] ヒト胃癌細胞株における細胞内Cl-濃度低下によって引き起こされるG1/S細胞周期遅延はMAPKを介して調節される (2008)
  • Author(s): 宮崎裕明,大澤るみ,新里直美,丸中良典
  • Organizer: 第3回トランスポーター研究会
  • Place of Presentation: 京都
• [Presentation] Intracellular chloride is a key regulator of the G1/S transition in MKN28 human gastric cancer cell. (2008)
  • Author(s): Miyazaki, H., Ohsawa, R., Shiozaki, A., Niisato, N., and Marunaka, Y.
  • Organizer: Beatson International Cancer Conference
  • Place of Presentation: Glasgow、Scotland
• [Presentation] 調節性容積減少(RVD)によって引き起こされる細胞内Cl-濃度低下は細胞内シグナルとして機能する (2008)
  • Author(s): 宮崎裕明,新里直美,西尾恭介,丸中良典
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡
• [Presentation] ヒト胃癌細胞株において細胞内Cl-濃度はG1/S細胞周期チェックポイントを制御する (2008)
  • Author(s): 宮崎裕明,大澤るみ,塩崎敦,新里直美,丸中良典
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] 骨芽細胞におけるクロライド依存的な細胞周期調節 (2007)
  • Author(s): 宮崎裕明,牧昌弘,中島謙一,新里直美,丸中良典
  • Organizer: 第100回近畿生理学談話会
  • Place of Presentation: 津