細胞生理学/生理学教室(細胞生理学部門)

細胞生理学HP http://kpum-molecular-cell-physiology.info/index.html

大学院科目名 細胞生理学
医学部教室名
生理学教室(細胞生理学部門)
スタッフ
教授  丸中 良典
 
 
特任教授    桑原 厚和
特任教授    中張 隆司
特任教授    新里 直美
准教授     宮崎 裕明
講師      樽野 陽幸
講師      細木 誠之
特任講師    中島 謙一
特任講師    桑原 裕子
助教      加塩 麻紀子
研究内容
1)ホルモンおよび浸透圧による上皮イオン輸送制御機構
 癌細胞増殖制御機構
 神経突起伸長機構
 クロライドイオンの生理活性特に、癌細胞増殖機構/神経突起伸長機構と細胞骨格形成機構におけるクロライドイオンの生理活性解明を研究テーマの中心とし、如何に細胞内クロライドイオン濃度が制御され、クロライドイオンが如何にして癌細胞増殖を調節し、また細胞骨格形成を調節しているかの分子メカニズムの解明を行っている。

2)副腎皮質ホルモンである電解質コルチコイド(アルドステロン)の Non Genomic Action の新たなる制御分子解明に係わる研究および細胞外浸透圧感受機構解明に係わる研究も推進している。この制御機構にもクロライドイオンが関与していることを解明した。
 
3)Calcium Homeostasis Modulator(CALHM)イオンチャネル
 CALHM1は遅発性アルツハイマー病発症に関わるイオンチャネル遺伝子として近年同定され(Dreses-Werringloer et al., Cell, 2008)、神経細胞の興奮性(Ma et al., PNAS, 2012)や神経伝達(Taruno et al., Nature, 2013)等、重要な生理的役割の一端が明らかとなってきた。ヒトでCALHM1と5つのホモログはCALHM遺伝子ファミリーを形成している。我々は、CALHMイオンチャネルの更なる生理的役割を解明すべく、分子・個体レベルでのCALHM分子の機能を分子生物学的手法・電気生理学的手法・Ca2+イメージング・免疫組織化学・遺伝子改変動物を駆使して体系的な解析を進めている。
 
4)味覚情報の抽出・処理・統合機構
 味覚は、舌にある味蕾の細胞が飲食物に含まれる化学物質を味覚情報として抽出・処理・統合し、求心性味神経へと情報伝達を行う化学感覚である。我々は、味覚コーディングの仕組みを分子レベルで解明すべく研究を行っている。先行研究で、上記CALHM1イオンチャネルが甘味・苦味・旨味の神経伝達に必須の分子である事を解明した(Taruno et al., Nature, 2013; Taruno et al., BioEssays, 2013)。
 
大学院生募集:これらの研究に参画を希望する大学院生を募集している。
 なお、研究業績に関しては、下記参照のこと。
研究業績
 Nakajima K, MARUNAKA Y
Intracellular chloride ion concentration in differentiating neuronal cell and its role in growing neurite
                 Biochem Biophys Res Commun(in press)
 
Taruno A, Kashio M, Sun H, Kobayashi K, Sano H, Nambu A, MARUNAKA Y
Adeno-associated virus-mediated gene transfer into taste cells in vivo
Chemical Senses(in press)
 
Pezzotti G, McEntire BJ, BockR, Zhu W, Boschetto F, Rondinella A, Marin E, MARUNAKA Y, Adachi T, Yamamoto T, Kanamura N, Bal BS
In situ spectroscopic screening of osteosarcoma living cells on stoichiometry-modulated silicon nitride bioceramic surfaces ACS Biomater Sci Eng 2(7): 1121-1134, 2016                    
 
Pezzotti G, Adachi T, Gasparutti I, Vincini G, Zhu W, Boffelli M, Rondinella A, Marin E, Ichioka H, Yamamoto T, MARUNAKA Y, Kanamura N
Vibrational monitor of early demineralization in tooth enamel after in vitro exposure to phosphoridic liquidSpectrochimica
Acta Part A Molecular and Biomolecular Spectroscopy173:19-33, 2016
 
MARUNAKA Y, Marunaka R, Sun H, Yamamoto T, Kanamura N, Taruno A
Na+homeostasis by epithelial Na+channel (ENaC) and Nax channel (Nax): cooperation of ENaC and NaxAnnals of Translational Medicine(in press)
                    
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
Quercetin is a useful medicinal compound showing various actions including control of blood pressure, neurite elongation and epithelial ion transport Current Med Chem
(in press)
 
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
Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma
 J Cancer7(11):1524-1533
 
Puppulin L, Miura Y, Casagrande E, Hasegawa M, MARUNAKA Y, Tone S, Sudo A, Pezzotti G
Validation of a protocol based on Raman and Infrared spectroscopies to nondestructively estimate the oxidative degradation of UHMWPE used in total joint arthroplasty. Acta Biomaterialia38:168-178, 2016                            
 
Tanaka S, Hosogi S, Sawabe Y, Shimamoto C, Matsumura H, Inui T, MARUNAKA Y, Nakahari T
PPARα activation of NOS1 via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in enhancement of Ca2+-regulated exocytosis
 Biomed Res37:167-178, 2016
 
Kimura T, Hashimoto Y, Tanaka M, Asano M, Yamazaki M, Oda Y, Toda H, MARUNAKA Y, Nakamura N, Fukui M
Sodium-chloride Difference and Metabolic Syndrome: A Population-based Large-scale Cohort Study
Internal Medicine (in press)
 
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 .
Silicon nitride bioceramics induce chemically driven lysis in porphyromonas gingivalis.
Langmuir. 32:3024-3035, 2016

Tsuji T, Matsuo K, Nakahari T,MARUNAKA Y, Yokoyama T
Structural basis of the Inv compartment and ciliary abnormalities in inv/nphp2 mutant mice
Cytoskeleton 73:45-56, 2016
 
Sasamoto K, Niisato N, Taruno A, MARUNAKA Y
Simulation of Cl-secretion in epithelial tissues: New methodology estimating activity of electro-neutral Cl-transporter
Frontiers in Physiology 6:370, 2015
 
Pezzotti G, Puppulin L, La Rosa A, Boffelli M, Zhu W, McEntire BJ, Hosogi S, Nakahari T, MARUNAKA Y
Effect of pH and monovalent cations on the Raman spectrum of water: Basics revisited and application to measure concentration gradients at water/solid interface in Si3N4 biomaterial
Chemical Physics 463:120-136, 2015
 
Ochi F, Shiozaki A, Ichikawa D, Fujiwara H, Nakashima S, Takemoto K, Kosuga T, Konishi H, Komatsu S, Okamoto K, Kishimoto M, MARUNAKA Y, Otsuji E
Carbonic anhydrase XII as an independent prognostic factor in advanced esophageal squamous cell carcinoma
J Cancer 6:922-929, 2015
 
Pezzotti G, Boffelli M, Miyamori D, Uemura T, MARUNAKA Y, Zhu W, Ikegaya H
Raman spectroscopy of human skin: looking for a quantitative algorithm to reliably estimate human age
J Biomed Optics 20:65008, 2015
 
Fukuda T, Fukui M, Tanaka M, Senmaru T, Iwase H, Yamazaki M, Aoi W, Inui T, Nakamura N, MARUNAKA Y
Effect of Brazilian green propolis in patients with type 2 diabetes: A double blind randomized placebo controlled study
Biomedical Reports 3: 355-360, 2015

Pezzotti G, Zhu W, Boffelli M, AdachiT, Ichioka H, Yamamoto T, MARUNAKA Y, Kanamura N
Vibrational algorithms for quantitative crystallographic analyses of hydroxyapatite-based biomaterials: I, Theoretical foundations
Analytical and Bioanalytical Chemistry 407:3325-42, 2015

Tomoda A, MARUNAKA Y, Eaton DC, Dinudom A
Membrane Transport: Ionic Environments, Signal Transduction, and Development of Therapeutic Targets
BioMed Res Int 2015:581626, 2015

MARUNAKA Y
Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function
World J Diabetes 6:125-135, 2015
 
Hatano R, Akiyama K, Tamura A, Hosogi S, MARUNAKA Y, Caplan MJ, Ueno Y, Tsukita S, Asano S.
Knockdown of ezrin causes intrahepatic cholestasis by the dysregulation of bile fluidity in the bile duct epithelium.
Hepatology 61:1660-71, 2015

Shiozaki A, Ichikawa D, Fujiwara H, Otsuji E, MARUNAKA Y
Progress in Cellular Physiological Researches on Esophageal Cancer
Journal of Tumor 2:252-256, 2014

Tanaka S, Sugiyama N, Takahashi Y, Mantoku D, Sawabe Y, Kuwabara H, Nakano
T, Shimamoto C, Matsumura H, MARUNAKA Y, Nakahari T
PPARα autocrine regulation of Ca2+-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.
Am J Physiol Gastrointest Liver Physiol 307:G1169-1179, 2014

Sun H, Niisato N, Inui T, MARUNAKA Y
Insulin is involved in transcriptional regulation of NKCC and CFTR Cl- channel through PI3K activation and ERK inactivation in renal epithelial cells
J Physiol Sci 64:433-443, 2014

Aoi W, MARUNAKA Y
Importance of pH homeostasis in metabolic health and diseases: crucial role of membrane proton transport
BioMed Res Int. 2014:598986, 2014

Yuan Y, Wang X, Lu X, MARUNAKA Y, Wang X
Effect of Coptidis Rhizoma extracts in a water-based solution on insulin resistance in 3T3-L1 adipocytes
Biomed Res 35:321-327, 2014

MARUNAKA Y
Characteristics and pharmacological regulation of epithelial Na+ channel (ENaC) and epithelial Na+ transport
J Pharmacol Sci 126:21-36 2014

Shiozaki A, Takemoto K, Ichikawa D, Kosuga T, Konishi H, Komatsu S, Fujiwara H, Okamoto K, Kishimoto M, MARUNAKA Y, Otsuji E
The K-Cl cotransporter KCC3 as an independent prognostic factor in human esophageal squamous cell carcinoma
BioMed Res Int 2014:936401, 2014
 
Shiozaki A, Ichikawa D, Takemoto K, Nako Y, Nakashima S, Shimizu H, Kitagawa M, Kosuga T, Konishi H, Komatsu S, Fujiwara H, Okamoto K, MARUNAKA Y, Otsuji E
Efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells-An in vivo evaluation
BioMed Res Int 2014:707089, 2014

Takemoto K, Shiozaki A, IchikawaD, Komatsu S, Konishi H, Nako Y, Murayama Y, Kuriu Y, Nakanishi M, Fujiwara H, Okamoto K, Sakakura C, Nakahari T, MARUNAKA Y, Otuji E
Evaluation of the efficacy of peritoneal lavage with distilled water in colorectal cancer surgery - in vitro and in vivo study
J Gastroenterol 50:287-97, 2015

Shiozaki A, Nako Y, Ichikawa D, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, MARUNAKA Y, Otsuji E
Role of the Na+/K+/2Cl- cotransporter NKCC1 in cell cycle progression in human esophageal squamous cell carcinoma
World Journal of Gastroenterology 20:6844-59, 2014

Sun H, Niisato N, Nishio K, Hamilton KL, MARUNAKA Y
Distinct action of flavonoids, myricetin and quercetin, on epithelial Cl- secretion : useful tools as regulators of Cl- secretion
BioMed Res Int 2014:902735, 2104

MARUNAKA Y
Importance of expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells
Respiratory Physiol Neurobiol 196:39-42, 2014

Hayata H, Miyazaki H, Niisato N, Yokoyama N, MARUNAKA Y
Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance
Biochem Biophys Res Commun 445:170-174, 2014

Hosogi S, Kusuzaki K, Inui T, Wang X, MARUNAKA Y.
Cytosolic chloride ion is a key factor in lysosomal acidification and function of autophagy in human gastric cancer cell
J Cell Mol Med 18:1124-1133, 2014

Shiozaki A, Ishikawa D, Otsuji E, MARUNAKA Y
Cellular Physiological Approach for Treatment of Gastric Cancer
World Journal of Gastroenterology 20:11560-6, 2014 Sep

MARUNAKA Y
Roles of ionic environments in growth of human cancer cell and potentials of ion transporter blockers in cancer therapies
J Gastrointestinal & Digestive System 3:163, 2014

Aoi W, MARUNAKA Y
The importance of regulation of body fluid pH in the development and progression of metabolic diseases
Advances in Medicine and Biology vol.77, pp. 177-189, 2014 Nova Publishers

MARUNAKA Y, Yoshimoto K, Aoi W, Hosogi S, Ikegaya H
Low pH of interstitial fluid around hippocampus of the brain in diabetic OLETF rats
Molecular and Cellular Therapies 2:6, 2014

Kitagawa M, Niisato N, Shiozaki A, Ohta-Fujimoto M, Hosogi S, Miyazaki H, Ichikawa D, Otsuji E, MARUNAKA Y
A regulatory role of K+-Cl- cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells
Arch Biochem Biophys 539:92-98, 2013

Tanaka S, Tanaka R, Harada S, Kohda Y, Matsumura H, Shimamoto C, Sawabe Y, MARUNAKA Y, Kuwabara H, Takahashi Y, Ito S, Nakahari T
A PKG inhibitor increases Ca2+-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition
Am J Physiol Gastrointest Liver Physiol 304:G773-G780, 2013

Aoi W, Hosogi S, Niisato N, Yokoyama N, Hayata H, Miyazaki H, Kusuzaki K, Fukuda T, Fukui M, Nakamura N, MARUNAKA Y
Improvement of insulin resistance, blood pressure and interstitial pH in early developmental stage of insulin resistance in OLETF rats by intake of propolis extracts
Biochem Biophys Res Commun 432:650-653, 2013

Hosogi S, Miyazaki H, Nakajima K, Ashihara E, Niisato N, Kusuzaki K, MARUNAKA Y
An Inhibitor of Na+/H+ Exchanger (NHE), Ethyl-Isopropyl Amiloride (EIPA), Diminishes Proliferation of MKN28 Human Gastric Cancer Cells by Decreasing the Cytosolic Cl-Concentration via DIDS-Sensitive Pathways.
Cell Physiol Biochem. 30:1241-1253, 2012.

Nako Y, Shiozaki A, Ichikawa D, Komatsu S, Konishi H, Iitaka D, Ishii H, Ikoma H, Kubota T, Fujiwara H, Okamoto K, Ochiai T, Nakahari T, MARUNAKA Y, Otsu E
Enhancement of the cytocidal effects of hypotonic solution using a chloride channel blocker in pancreatic cancer cells
Pancreatology 12:440-448, 2012.

Nakajima K, Niisato N, MARUNAKA Y
Enhancement of tubulin polymerization by Cl--induced blockade of intrinsic GTPase
Biochem Biophys Res Commun 425:225-229, 2012

Nagao H, Nakajima K, Niisato N, Hirota R, Bando H, Sakaguchi H, Hisa Y, MARUNAKA Y
K+-Cl- cotransporter 1 (KCC1) negatively regulates NGF-induced neurite outgrowth in PC12 cells
Cell Physiol Biochem 30:538-551, 2012

Niisato N, Ohta M, Eaton DC, MARUNAKA Y
Hypotonic stress upregulates beta- and gamma-ENaC expression through suppression of ERK by inducing MKP-1.
Am J Physiol (Renal Physiol) 303:F240-252, 2012

Kusuzaki K, Hosogi S, Ashihara E, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Sudo A, Uchida A, Murata H, Baldini N, Fais S, MARUNAKA Y
Translational Research of Photodynamic Therapy with Acridine Orange which Targets Cancer Acidity.
Current Pharmaceutical Design 18:1414-1420, 2012.

Kusuzaki K, Hosogi S, Ashihara E, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Sudo A, Uchida A, Murata H, Baldini N, Fais S, MARUNAKA Y
New Concept of Limb Salvage Surgery in Musculoskeletal Sarcomas with Acridine Orange Therapy
In: Sarcoma: Symptoms, Causes and Treatments (Editor: Butler EJ)pp.124-137, Nova Science Publishers, New York, 2012

Niisato N, MARUNAKA Y
Sensing mechanism of stretch activated ion channels Mechanically Gated Channels and mechanisms of their regulation / Mechanosensitivity in Cells and Tissues
Springer 6:189-213, 2012

Komatani-Tamiya N, Daikoku E, Takemura Y, Shimamoto C, Nakano T, Iwasaki Y, Matsumura H, MARUNAKA Y, Nakahari T
Procaterol-stimulated increases in ciliary bend amplitude and ciliary beat frequency in mouse bronchioles. 
Cell Physiol Biochem 29:511-22, 2012

Iitaka D, Shiozaki A, Ichikawa D, Kosuga T, Komatsu S, Okamaoto K, Fujiwara H, Ishii H, Nakahari T, MARUNAKA Y, Otsuji E. Blockade of chloride ion transport enhances the cytocidal effect of hypotonic solution in gastric cancer cells.
J Surgical Res 176:524-534, 2012

Nakajima K, Niisato N, MARUNAKA Y
Genistein enhances the NGF-induced neurite outgrowth.
Biomed Res 32:351-356, 2011
Shiozaki A, Otsuji E, MARUNAKA Y
Intracellular chloride regulates the G1/S cell cycle progression in gastric cancer cells
World J Gastrointest Oncol 3:119-122, 2011

MARUNAKA Y, Niisato N, Taruno A, Ohta M, Miyazaki H, Hosogi S, Nakajima K, Kusuzaki K, Ashihara E, Nishio K, Iwasaki Y, Nakahari T, Kubota T
Regulation of epithelial sodium transport via epithelial Na+ channel (ENaC)
J Biomed Biotechnol 2011:978196, 2011

Kosuga T, Shiozaki A, Ichikawa D, Fujiwara H, Komatsu S, Iitaka D, Tsujiura M, Morimura R, Takeshita H, Nagata H, Okamoto K, Nakahari T, MARUNAKA Y, Otsuji E
Pleural lavage with distilled water during surgery for esophageal squamous cell carcinoma
Oncology Reports 26:577-586, 2011

Nakajima K, Niisato N, MARUNAKA Y
Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na+/K+/2Cl- cotransporter
Cell Physiol Biochem 28:147-156, 2011

Hashimoto-Gotoh T, Iwabe N, Tsujimura A, Nakagawa M, MARUNAKA Y
KF-1 Ubiquitin Ligase: Anxiety Suppressor
Model Cell Biochem Biophys 60:69-75, 2011

Taruno A, MARUNAKA Y
Analysis of blocker-labeled channels reveals the dependence of recycling rates of ENaC on the total amount of recycled channels
Cell Physiol Biochem 26:925-934, 2010

Sawabe Y, Shimamoto C, Sakai A, Kuwabara H, Saad AH, Nakano T, Takitani K, Tamai H, Mori H, MARUNAKA Y, Nakahari T.
PPAR-alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea pig antral mucous cells.
Exp Physiol 95:858-868, 2010.
Ohsawa R, Miyazaki H, Niisato N, Shiozaki A, Iwasaki Y, Otsuji E, MARUNAKA Y.
Intracellular chloride regulates cell proliferation through the activation of stress-activated protein kinases in MKN28 human gastric cancer cells.
J Cell Physiol 223:764-770, 2010

Hiraoka K, Miyazaki H, Niisato N, Iwasaki Y, Kawauchi A, Miki T, MARUNAKA Y.
Chloride ion modulates cell proliferation of human androgen-independent prostatic cancer cell.
Cell Physiol Biochem 25:379-388, 2010

Asano J, Niisato N, Nakajima K, Miyazaki H, Yasuda M, Iwasaki Y, Hama T, Dejima K, Hisa Y, MARUNAKA Y.
Quercetin stimulates NKCC1 via a PTK-dependent mechanism in human airway epithelium.
Am J Resp Cell Mol Biol 41:688-695, 2009

Taruno A, Niisato N, MARUNAKA Y.
Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells.
Am J Physiol Renal Physiol 294:F177-186, 2008

Tokuda S, Shimamoto C, Yoshida H, Murao H, Kishima G, Ito S, Kubota T, Hanafusa T, Sugimoto T, Niisato N, MARUNAKA Y, Nakahari T.
HCO3- dependent pHi recovery and overacidification induced by NH4+ pulse in rat lung alveolar type II cells: HCO3- dependent NH3 excretion from lungs
Pfluegers Arch (Eur J Physiol) 455:223-239, 2007.

Taruno A, Niisato N, MARUNAKA Y.
Hypotonicity stimulates renal epithelial sodium transport by activating JNK via receptor tyrosine kinases.
Am J Physiol Renal Physiol 293:F128-138, 2007.

Miyazaki H, Shiozaki A, Niisato N, MARUNAKA Y.
Physiological significance of hypotonicity-induced regulatory volume decrease: reduction in intracellular Cl- concentration acting as an intracellular signaling.
Am J Physiol Renal Physiol 292:F1411-1417, 2007.

Yasuda M, Niisato N, Miyazaki H, Hama T, Dejima K, Hisa Y, MARUNAKA Y.
Epithelial ion transport of human nasal polyp and paranasal sinus mucosa. Am J Respir Cell Mol Biol 36:466-472, 2007.

Saad AH, Shimamoto C, Nakahari T, Fujiwara S, Katsu K, MARUNAKA Y.
cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells.
Am J Physiol Gastrointest Liver Physiol 290:G1138-G1148, 2006
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