Noninvasive assay development of interstitial fluid pH and bicarbonate concentration by MRI and Raman spectrum

2016 Fiscal Year Annual Research Report

• Project/Area Number: 15K15034
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 丸中 良典 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00127036)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 間質液 / pH / 糖尿病 / ラマン分光 / アルツハイマー型認知症 / 核磁気共鳴 / 重炭酸イオン / インスリン抵抗性

Outline of Annual Research Achievements

２０１２年における糖尿病患者数は世界で３億７千万人、我国で2千万人にものぼる。また、２型糖尿病患者におけるアルツハイマー型認知症発症のリスクが高いことも報告されている。我々は、２型糖尿病での病態の本体ともいえるインスリン抵抗性の発症およびアルツハイマー型認知症におけるアミロイドベータ生成に組間質液pH低下が関与していることを明らかにした。従って、ヒト脳間質液pH測定は糖尿病・アルツハイマー型認知症の予防医学的診断に重要な役割を担っているが、ヒトの脳内組織間質液pHの非侵襲的測定法は未だ開発されていない。間質液重炭酸イオン濃度測定は間質液pH低下原因解明のため重要であるが、間質液HCO3-濃度非侵襲的測定法も未だ開発されていない。【研究目的】核磁気共鳴画像法およびラマン分光法をを用いて、間質液pHおよび重炭酸イオン濃度の非侵襲的測定法を開発する。【研究結果】まず第一段階として、pHおよび重炭酸イオン濃度を溶液系・細胞系を用いて測定した。その結果、pHおよび重炭酸イオン濃度を測定し得る測定法の開発に成功した。即ち、ラマン分光1016cm-1スペクトル強度が重炭酸イオン濃度変化に応じて線形的に変化することが明らかとなった。一方、二酸化炭素濃度に依存してスペルトル強度が変わりうるバンドをほぼ特定した（論文投稿準備中）。重炭酸イオンおよび二酸化炭素濃度の測定が可能となったことにより、pHの定量的値が計測可能となった。この成果をもとに、ヒト間質液pH測定法の開発を現在進めているところである。

Research Products

• [Journal Article] Raman micro-spectroscopy as a viable tool to monitor and estimate the ionic transport in epithelial cells (2017)
  • Author(s): Puppulin P, Pezzotti G, Sun H, Hosogi S, Nakahari T, Inui T, Kumamoto Y, Tanaka H, MARUNAKA Y
  • Journal Title: Scientific Reports Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A low [Ca2+]i-induced enhancement of cAMP-activated ciliary beating by PDE1A inhibition in mouse airway cilia (2017)
  • Author(s): Kogiso H, Hosogi S, Ikeuchi Y, Tanaka S, Shimamoto C, Matsumura H, Nakano T, Sano K, Inui T, MARUNAKA Y, Nakahari T
  • Journal Title: Pflugers Archiv - Eur J Physiol Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cytosolic Cl- affects the anticancer activity of paclitaxel in the gastric cancer cell line, MKN28 cell (2017)
  • Author(s): Tanaka S, Miyazaki H, Shiozaki A, Ichikawa D, Otsuji E, MARUNAKA Y
  • Journal Title: Cell Physiol Biochem Volume: 42 Pages: 68-80
  • DOI: 10.1159/000477116
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Actions of quercetin, a flavonoid, on ion transporters: its physiological roles (2017)
  • Author(s): MARUNAKA Y
  • Journal Title: Annals of the New York Academy of Sciences Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor (2017)
  • Author(s): Shiozaki A, Kudou M, Ichikawa D, Fujiwara H, Shimizu H, Ishimoto T, Arita T, Kosuga T, Konishi H, Komatsu S, Okamoto K, MARUNAKA Y, Otsuji E
  • Journal Title: J Gastroenterol Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1007/s00535-017-1338-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Analysis of aprotinin, a protease inhibitor, action on the trafficking of epithelial Na+ channels (ENaC) in renal epithelial Ccells using a mathematical model (2017)
  • Author(s): Sasamoto K, Marunaka R, Niisato N, Sun H, Taruno A, Pezzottia G, Yamamoto T, Kanamura N, Zhu W, Nishio K, Inuia T, Eaton DC, MARUNAKA Y
  • Journal Title: Cell Physiol Biochem Volume: 41 Pages: 1865-1880
  • DOI: 10.1159/000471934
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Heat shock exerts anticancer effects on liver cancer via autophagic degradation of aquaporin (2017)
  • Author(s): Kudou M, Shiozaki A, Kosuga T, Shimizu H, Ichikawa D, Konishi H, Morimura R, Komatsu S, Ikoma H, Fujiwara H, Okamoto K, MARUNAKA Y, Otsuji E
  • Journal Title: Int J Oncol Volume: 50 Pages: 1857-1867
  • DOI: 10.3892/ijo.2017.3940
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulation of osmolality for cancer treatment (2017)
  • Author(s): Shiozaki A, Ichikawa D, Kosuga T, MARUNAKA Y, Otsuji E.
  • Journal Title: J Physiol Sci Volume: 67 Pages: 353-360
  • DOI: 10.1007/s12576-017-0528-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Actions of quercetin, a polyphenol, on blood Pressure (2017)
  • Author(s): MARUNAKA Y, Marunaka R, Sun H, Yamamoto T, Kanamura N, Inui T, Taruno A.
  • Journal Title: Molecules Volume: 22 Pages: E209
  • DOI: 10.3390/molecules22020209
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hypotonicity activates a voltage-dependent membrane conductance in N2a neuroblastoma cells (2017)
  • Author(s): Taruno A, MARUNAKA Y
  • Journal Title: Biochem Biophys Res Commun Volume: 484 Pages: 331-335
  • DOI: 10.1016/j.bbrc.2017.01.118
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Na+/H+ exchanger 1 has tumor suppressive activity and prognostic value in esophageal squamous cell carcinoma (2017)
  • Author(s): Ariyoshi Y, Shiozaki A, Ichikawa D, Shimizu H, Kosuga T, Konishi H, Komatsu S, Fujiwara H, Okamoto K, Kishimoto M, MARUNAKA Y, Otsuji E
  • Journal Title: Oncotarget Volume: 8 Pages: 2209-2223
  • DOI: 10.18632/oncotarget
  • Peer Reviewed
• [Journal Article] Enhanced alcohol-drinking behavior associated with active ghrelinergic and serotoninergic neurons in the lateral hypothalamus and amygdala (2017)
  • Author(s): Yoshimoto K, Nagao M, Watanabe Y, Yamaguchi T, Ueda S, Kitamura Y, Nishimura K, Inden M, MARUNAKA Y, Hattori H, Murakami K, Tokaji M, Ochi K
  • Journal Title: Pharmacol Biochem Behavior Volume: 153 Pages: 1-11
  • DOI: 10.1016/j.pbb.2016.12.001
  • Peer Reviewed
• [Journal Article] Expression and role of anion exchanger 1 in esophageal squamous cell carcinoma (2017)
  • Author(s): Shiozaki A, Kudou M, Ichikawa D, Shimizu H, Arita T, Kosuga T, Konishi H, Komatsu S, Fujiwara H, Okamoto K, Kishimoto M, MARUNAKA Y, Otsuji E
  • Journal Title: Oncotarge Volume: 8 Pages: 17921-17935
  • DOI: 10.18632/oncotarget.14900
  • Peer Reviewed
• [Journal Article] Adeno-associated virus-mediated gene transfer into taste cells in vivo (2017)
  • Author(s): Taruno A, Kashio M, Sun H, Kobayashi K, Sano H, Nambu A, MARUNAKA Y
  • Journal Title: Chemical Senses Volume: 42 Pages: 69-78
  • DOI: 10.1093/chemse/bjw101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Vibrational monitor of early demineralization in tooth enamel after in vitro exposure to phosphoridic liquid (2017)
  • Author(s): Pezzotti G, Adachi T, Gasparutti I, Vincini G, Zhu W, Boffelli M, Rondinella A, Marin E, Ichioka H, Yamamoto T, MARUNAKA Y, Kanamura N
  • Journal Title: Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy Volume: 173 Pages: 19-33
  • DOI: 10.1016/j.saa.2016.08.036
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Intracellular chloride ion concentration in differentiating neuronal cell and its role in growing neurite (2016)
  • Author(s): Nakajima K, MARUNAKA Y
  • Journal Title: Biochem Biophys Res Commun Volume: 479 Pages: 338-342
  • DOI: 10.1016/j.bbrc.2016.09.075
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In situ spectroscopic screening of osteosarcoma living cells on stoichiometry-modulated silicon nitride bioceramic surfaces (2016)
  • Author(s): Pezzotti G, McEntire BJ, BockR, Zhu W, Boschetto F, Rondinella A, Marin E, MARUNAKA Y, Adachi T, Yamamoto T, Kanamura N, Bal BS
  • Journal Title: ACS Biomater Sci Eng Volume: 2 Pages: 1121-1134
  • DOI: 10.1021/acsbiomaterials.6b00126
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Na+ homeostasis by epithelial Na+ channel (ENaC) and Nax channel (Nax): cooperation of ENaC and Nax (2016)
  • Author(s): MARUNAKA Y, Marunaka R, Sun H, Yamamoto T, Kanamura N, Taruno A
  • Journal Title: Annals of Translational Medicine Volume: 4 Pages: S11
  • DOI: 10.21037/atm.2016.10.42
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Quercetin is a useful medicinal compound showing various actions including control of blood pressure, neurite elongation and epithelial ion transport (2016)
  • Author(s): MARUNAKA Y, Niisato N, Miyazaki H, Nakajima K, Taruno A, Sun H, Marunaka R, Okui M, Yamamoto T, Kanamura N, Kogiso H, Ikeuchi Y, Kashio M, Hosogi S, Nakahari T
  • Journal Title: Current Med Chem Volume: 23 Pages: 1-12
  • DOI: 10.2174/0929867323666160919095043
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibition of regulatory volume decrease enhances the cytocidal effect of hypotonic shock in hepatocellular carcinoma (2016)
  • Author(s): Kudou M, Shiozaki A, Kosuga T, IchikawaD, Konishi H, Morimura R, Komatsu S, Ikoma H, Fujiwara H, Okamoto K, Hosogi S, Nakahari T, MARUNAKA Y, Otsuji E
  • Journal Title: J Cancer Volume: 7 Pages: 1524-1533
  • DOI: 10.7150/jca.15181
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Validation of a protocol based on Raman and Infrared spectroscopies to nondestructively estimate the oxidative degradation of UHMWPE used in total joint arthroplasty (2016)
  • Author(s): Puppulin L, Miura Y, Casagrande E, Hasegawa M, MARUNAKA Y, Tone S, Sudo A, Pezzotti G
  • Journal Title: Acta Biomaterialia Volume: 38 Pages: 167-178
  • DOI: 10.1016/j.actbio.2016.04.040
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] PPARα activation of NOS1 via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in enhancement of Ca2+-regulated exocytosis (2016)
  • Author(s): Tanaka S, Hosogi S, Sawabe Y, Shimamoto C, Matsumura H, Inui T, MARUNAKA Y, Nakahari T
  • Journal Title: Biomed Res Volume: 37 Pages: 167-178
  • DOI: 10.2220/biomedres.37.167
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sodium-chloride difference and metabolic syndrome: a population-based large-scale cohort Study (2016)
  • Author(s): Kimura T, Hashimoto Y, Tanaka M, Asano M, Yamazaki M, Oda Y, Toda H, MARUNAKA Y, Nakamura N, Fukui M
  • Journal Title: Internal Medicine Volume: 55 Pages: 3085-3090
  • DOI: 10.2169/internalmedicine.55.7000
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Silicon nitride bioceramics induce chemically driven lysis in porphyromonas gingivalis (2016)
  • Author(s): Pezzotti G, Bock RM, McEntire BJ, Jones E, Boffelli M, Zhu W, Baggio G, Boschetto F, Puppulin L, Adachi T, Yamamoto T, Kanamura N, MARUNAKA Y, Bal BS
  • Journal Title: Langmuir Volume: 32 Pages: 3024-3035
  • DOI: 10.1021/acs.langmuir.6b00393
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Structural basis of the Inv compartment and ciliary abnormalities in inv/nphp2 mutant mice (2016)
  • Author(s): Tsuji T, Matsuo K, Nakahari T, MARUNAKA Y, Yokoyama T
  • Journal Title: Cytoskeleton Volume: 73 Pages: 45-56
  • DOI: 10.1002/cm.21264
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Regulation of body environments by epithelial ion transport (2017)
  • Author(s): MARUNAKA Y
  • Organizer: The 94th Annual Meeting of the Physiological Society of Japan.
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-28 – 2017-03-30
  • Invited
• [Presentation] Neurotransmission of taste mediated by calcium homeostasis modulator ion channels (2017)
  • Author(s): Taruno A, MARUNAKA Y
  • Organizer: The 94th Annual Meeting of the Physiological Society of Japan.
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-28 – 2017-03-30
  • Invited
• [Presentation] Insulin and the CFTR Chloride Channel. (2016)
  • Author(s): MARUNAKA Y, Niisato N, Hongxin Sun, Inui T.
  • Organizer: The 30th Annual North American Cystic Fibrosis Conference.
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2016-10-27 – 2016-10-29
  • Int'l Joint Research / Invited
• [Presentation] How do chloride and hydrogen ions regulate body function? (2016)
  • Author(s): MARUNAKA Y
  • Organizer: 2016 International Conference of Physiological Science
  • Place of Presentation: Beijing, China
  • Year and Date: 2016-09-25 – 2016-09-28
  • Int'l Joint Research / Invited
• [Presentation] Homologous CALHM subunits assemble to form a novel voltage-gated ATP channel (2016)
  • Author(s): Taruno A, Miyazaki H, Niisato N, Hongxin S, Kashio M, MARUNAKA Y.
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20 – 2016-07-22
  • Invited
• [Presentation] ブラジル産プロポリスの糖尿病に対する効果 (2016)
  • Author(s): 丸中良典
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-10 – 2016-06-12
  • Invited
• [Presentation] Purinergic neurotransmission of taste by CALHM channel (2016)
  • Author(s): Taruno A, MARUNAKA Y.
  • Organizer: 17th ISOT JASTS 50th Annual Meeting
  • Place of Presentation: Yokohama
  • Year and Date: 2016-06-05 – 2016-06-09
  • Int'l Joint Research / Invited
• [Presentation] How are Cl- and H+ involved in diseases such as hypertension, diabetes and cancer? (2016)
  • Author(s): MARUNAKA Y
  • Organizer: International Symposium on Ion Channels, Transporters and Signal Transduction
  • Place of Presentation: 京都
  • Year and Date: 2016-05-21 – 2016-05-21
  • Int'l Joint Research / Invited
• [Remarks] 京都府立医科大学 大学院 医学研究科 細胞生理学
  • URL: http://kpum-molecular-cell-physiology.info/index.html