Role of membrane potential in phagocytes

• Project/Area Number: 24590277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Osaka University
• Principal Investigator: Okochi Yoshifumi 大阪大学, 医学(系)研究科(研究院), 助教 (90435818)
• Co-Investigator(Renkei-kenkyūsha): Umemoto Eiji 大阪大学, 大学院医学系研究科, 准教授 (90452440) ; Sakimura kenji 新潟大学, 脳研究所, 教授 (40162325) ; Okamura Yasushi 大阪大学, 大学院医学系研究科, 教授 (80201987) ; Tsutsui Hidekazu 北陸先端科学技術大学院大学, 准教授 (30392038)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プロトンチャネル / 炎症 / 好中球 / 脱顆粒 / 貪食細胞 / 活性酸素 / pH / 膜電位 / エキソサイトーシス / 走化性

Outline of Final Research Achievements

Voltage-gated proton channel regulates intracellular pH and membrane potential in phagocytes. We investigated the function of proton channel in neutrophils that are important immune cell in host defense. We found that proton channel negatively regulates the release of azurophil granules in neutrophils, which contain myeloperoxidase producing hypochlorous acid and degradative enzymes. We also found that proton channel deficient mice exhibit severer inflammation in lung than wild type mice upon fungal infection. These results suggest that proton channel suppresses inflammation through the inhibition of the granule release in neutrophils.

Research Products

• [Int'l Joint Research] Physiology & Experimental Medicine/Hospital for Sick Children(Canada)
• [Journal Article] The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release (2016)
  • Author(s): Okochi Y, Aratani Y, Adissu HA, Miyawaki N, Sasaki M, Suzuki K, Okamura Y.
  • Journal Title: J Leukoc Biol. Volume: 99 Issue: 1 Pages: 7-19
  • DOI: 10.1189/jlb.3hi0814-393r
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Functional diversity of voltage-sensing phosphatases (VSPs) in two urodele amphibians (2014)
  • Author(s): Mutua J, Jinno Y, Sakata S, Okochi Y, Ueno S, Tsutsui H, Kawai T, Iwao Y, Okamura Y.
  • Journal Title: Physiological Reports Volume: 2 Issue: 7 Pages: 1-13
  • DOI: 10.14814/phy2.12061
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] X-ray crystal structure of voltage-gated proton channel (2014)
  • Author(s): Takeshita K, Sakata S, Yamashita E, Fujiwara Y, Kawanabe A, Kurokawa T, Okochi Y, Matsuda M, Narita H, Okamura Y & Nakagawa A
  • Journal Title: Nat. Strucl. & Mol. Biol. Volume: (4) Issue: 4 Pages: 352-7
  • DOI: 10.1038/nsmb.2783
  • Peer Reviewed / Open Access
• [Journal Article] Autoimmune disorder phenotypes in HVCN1 gene deficient mice. (2013)
  • Author(s): Sasaki M, Tojo A, Okochi Y, Miyawaki N, Kamimura D, Yamaguchi A, Murakami M, Okamura Y.
  • Journal Title: Biochem J Volume: 450 Issue: 2 Pages: 295-301
  • DOI: 10.1042/bj20121188
  • Peer Reviewed
• [Journal Article] The cytoplasmic coiled-coil mediates cooperative gating temperature sensitivity in the voltage-gated H+ channel Hv1 (2012)
  • Author(s): Fujiwara Y, Kurokawa T, Takeshita K, Kobayashi M, Okochi Y, Nakagawa A & Okamura Y
  • Journal Title: Nat. Communi. Volume: 3 Issue: 1 Pages: 816-816
  • DOI: 10.1038/ncomms1823
  • Peer Reviewed
• [Presentation] The role of voltage-gated proton channel Hv1 in neutrophil chemotaxis (2016)
  • Author(s): Yoshifumi Okochi and Yasushi Okamura
  • Organizer: The 93rd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: sapporo
  • Year and Date: 2016-03-22
• [Presentation] Voltage-gated proton channel Hv1/VSOP inhibits granule exocytosis in neutrophils and inflammation (2015)
  • Author(s): Yoshifumi Okochi, Yasuaki Aratani, Hibret A. Adissu, Nana Miyawaki, Mari Sasaki, Kazuo Suzuk, Yasushi Okamura
  • Organizer: 8th Federation of the Asian and Oceanian Physiological Societies Cngress
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2015-11-23
  • Int'l Joint Research
• [Presentation] Multistep regulation of ROS production by voltage-gated proton channel Hv1/VSOP in neutrophils (2015)
  • Author(s): Yoshifumi Okochi, Yasuaki Aratani, Hibret A. Adissu, Nana Miyawaki, Mari Sasaki, Kazuo Suzuki, Yasushi Okamura
  • Organizer: the 92th annual meeting of the physiological society of japan
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21
• [Presentation] マウス精子における電位依存性ホスファターゼの機能 (2015)
  • Author(s): 河合 喬文、宮田 治彦、中西 広樹、坂田 宗平、有馬 大貴、宮脇 奈那、大河内 善史、崎村 建司、佐々木 雄彦、伊川 正人、岡村 康司
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21
• [Presentation] ミクログリアにおける電位依存性プロトンチャネルの機能 (2014)
  • Author(s): 河合 喬文、大河内 善史、宮脇 奈那、井村 誉史雄、古川 祐子、崎村 建司、小泉 修一、岡村 康司
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Analysis of the role of voltage-gated proton channel Hv1/VSOP in neutrophil chemotaxis (2014)
  • Author(s): Yoshifumi Okochi and Yasushi Okamura
  • Organizer: 第９１回日本生理学会大会
  • Place of Presentation: 鹿児島大学
• [Presentation] Metabolic phenotype in voltage-gated proton channels knockout mice (2014)
  • Author(s): Kawai Takafumi, Okochi Yoshifumi, Imura Yoshio, Furukawa Yuko, Miyawaki Nana, Sakimura Kenji, Koizumi Schuichi, Okamura Yasushi
  • Organizer: 第９１回日本生理学会大会
  • Place of Presentation: 鹿児島大学
• [Presentation] Autoimmune disorder phenotypes in Hvcn1-deficient mice (2013)
  • Author(s): Mari Sasaki, Akihiro Tojo, Yoshifumi Okochi, Nana Miyawaki, Daisuke Kamimura, Akihito Yamaguchi, Masaaki Murakami and Yasushi Okamura
  • Organizer: The 90th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: タワーホール船堀（東京）
• [Presentation] Subcellular localization of voltage-gated proton channel in primary cultured microglia (2013)
  • Author(s): Takafumi Kawai, Yoshio Imura, Shuichi Koizumi, Yoshifumi Okochi, Kenji Sakimura, Yasushi Okamura
  • Organizer: The 90th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: タワーホール船堀（東京）
• [Presentation] Physiological Genomic of Amphibian VSP: A Potential Molecular Mechanism of Electrical Block of Fertilization in Vertebrates (2013)
  • Author(s): Joshua Mutunga Mutua, Yuka Jinno, Shuichi Ueno, Souhei Sakata, Yoshifumi Okochi, Hidekazu, Tsutsui, Yasuhiro Iwao, Laurinda Jaffe, Yasushi Okamura
  • Organizer: The 90th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: タワーホール船堀（東京）
• [Remarks] 電位依存性プロトンチャネルHv1/VSOPは好中球の脱顆粒を抑制する
  • URL: http://physiology.jp/science-topic/17882/
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/phys2/okamura/
• [Remarks] 大阪大学統合生理学ホームページ
  • URL: http://www.med.osaka-u.ac.jp/pub/phys2/okamura/