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樋口 京一  ヒグチ ケイイチ

教員組織電話番号0263-37-2691
教育組織先鋭領域融合研究群 バイオメディカル研究所 ニューロヘルスイノベーション部門FAX番号0263-37-3428
職名特任教授メールアドレスkeiichih@shinshu-u.ac.jp
住所〒390-8621 松本市旭3-1-1ホームページURLhttp://www.shinshu-u.ac.jp/faculty/medicine/department/doctor/grdkarei/i-byotai/

更新日:2023/04/21

プロフィール

研究分野
加齢生物学
アミロイドーシス
キーワード:老化 , モデル動物 , アミロイドーシス
現在の研究課題
マウス特に老化促進モデルマウス(SAM)を用いた老化、寿命、老化病態の遺伝的要因の解析

アミロイド-シス発祥機構の分子生物学的研究

抗老化処方の検討
キーワード:抗老化 , 運動
リポタンパク質特にHDLの代謝調整の基礎的研究

所属学会
所属学会
日本基礎老化学会
International Society of Amyloidosis
日本病理学会
日本実験動物学会
日本臨床ストレス応答学会
老化促進モデルマウス学会
学歴
出身大学院
1984 , 京都大学 , 医学
1980 , 京都大学 , 農学

出身学校・専攻等(大学院を除く)
1978 , 京都大学 , 農学部

取得学位
医学博士
研究職歴等
研究職歴
2019- , 信州大学先鋭領域融合研究群バイオメディカル研究所ニューロヘルスイノベーション部門
2018- , 信州大学先鋭領域融合研究群バイオメディカル研究所神経難病学部門
2012- , 信州大学大学院医学系研究科疾患予防医科学系専攻 加齢生物学分野教授
1998- , 信州大学 教授(医学部付属加齢適応研究センター)
1989-1998 , 京都大学胸部疾患研究所 講師(老化生物学)
1986-1988 , アメリカ合衆国国立衛生研究所(NIH)心肺血液研究所分子病分野Visiting Fellow
1984-1989 , 京都大学結核研究所 助手(病理学)

留学歴
1986-1988 , 米国国立衛生研究所(NIH)国立心肺血液研究所(NHLBI)

研究活動業績

研究業績(著書・
発表論文等)
書籍等出版物
SAM(老化促進モデルマウス)『モデル動物の作成と維持』
エル・アイ・シー(東京) 2004
Author:樋口京一、森 政之。


分子生物学・免疫学キーワード辞典(第2版)
医学書院 2003
Author:樋口京一、森 政之


「分子シャペロンによる細胞機能制御」;アミロイド線維タンパク質、シュプリンガー・フェアラーク東京、単著、永田和宏・森正敬・吉田賢右編、pp164-174, 総頁数219頁中11頁を担当.
2001


「Les Amyloidoses」: Model of Amyloidosis of Senescence, Flammarion Medicine Science , 共著、G. Grateuau ,MD. Benson 他2名編集、K. Higuchi, H. Naiki, M. Hosokawa, T. Takada . pp138-145, 総頁数585頁中8頁を担当.
2000


論文
Suppression of mouse AApoAII amyloidosis progression by daily supplementation with oxidative stress inhibitors.
Oxid Med Cell Longev.,2019:126327 2019
Author:Dai J, Ding X, Miyahara H, Xu Z, Cui X, Igarashi1 Y, Sawashita J, Mori M, Higuchi K.


Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells
Oxid Med Cell Longev,2018:3181759 2018(Jun.)
Author:Huo J, Xu Z, Hosoe K, Kubo H, Miyahara H, Dai J, Mori M, Sawashita J, Higuchi K.


Amyloidosis-inducing activity of blood cells in mouse AApoAII amyloidosis.
Exp Anim.,67(2):105-115 2018(May)
Author:Ding X, Liu Y, Yang M, Li L, Miyahara H, Dai J, Xu Z, Matsumoto K, Mori M, Higuchi K, Sawashita J.


Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.
Sci Rep,8(1):5620 2018(Apr.)
Author:Yang M, Liu Y, Dai J, Li L, Ding X, Xu Z, Mori M, Miyahara H, Sawashita J, Higuchi K.


Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis.
J Proteomics,172:111-121 2018(Feb.)
Author:Miyahara H, Sawashita J, Ishikawa E, Yang M, Ding X, Liu Y, Hachiya N, Kametani F, Yazaki M, Mori M, Higuchi K.
Keywords:Amyloid


SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.
Neuropathology,(37):293-305 2017(Aug.)
Author:Akiguchi I, Pallàs M, Budka H, Akiyama H, Ueno M, Han J, Yagi H, Nishikawa T, Chiba Y, Sugiyama H, Takahashi R, Unno K, Higuchi K, Hosokawa M.
Keywords:Senescece Accelerated mouse


Caloric restriction reduces the systemic progression of mouse AApoAII amyloidosis.
PLoS One,12(2):e0172402 2017
Author:Li L, Sawashita J, Ding X, Yang M, Xu Z, Miyahara H, Mori M, Higuchi K.
Keywords:Amyloid


Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition.
Sci Rep. :,7(1):8253 2017
Author:Xu Z, Huo J, Ding X, Yang M, Li L, Dai J, Hosoe K, Kubo H, Mori M, Higuchi K, Sawashita J.


Serum amyloid A expression in the breast cancer tissue is associated with poor prognosis.
Yang M, Liu F, Higuchi K, Sawashita J, Fu X, Zhang L, Zhang L, Fu L, Tong Z, Higuchi K.,7(24):35843-35852 2016
Author:Yang M, Liu F, Higuchi K, Sawashita J, Fu X, Zhang L, Zhang L, Fu L, Tong Z, Higuchi K.
Keywords:Amyloid


The pathological and biochemical identification of possible seed-lesions of transmitted transthyretin amyloidosis after domino liver transplantation
J Pathol,in press 2016
Author:Yoshinaga T, Yazaki M, Sekijima Y, Kametani F, Miyashita K, Nishio S, Kanizawa Y, Hachiya N, Tanaka T, Kokudo N, Higuchi K, Ikeda S


The factors affecting adherence to a long-term interval walking training program in middle-aged and older people
J Appl Physiol (1985),118(5):595-603 2015
Author:Masuki S, Mori M, Tabara Y, Sakurai A, Hashimoto S, Morikawa M, Miyagawa K, Sumiyoshi E, Miki T, Higuchi K, Nose H; Shinshu University Genetic Research Consortium


Extracellular deposition of mouse senile AApoAII amyloid fibrils induced different unfolded protein responses in the liver, kidney, and heart
Lab Invest,95(3):320-333 2015
Author:Luo H, Sawashita J, Tian G, Liu Y, Li L, Ding X, Xu Z, Yang M, Miyahara H, Mori M, Qian J, Wang Y, Higuchi K


C-terminal sequence of amyloid-resistant type F apolipoprotein A-II inhibits amyloid fibril formation of apolipoprotein A-II in mice
Proc Natl Acad Sci U S A,12(8):E836-845 2015
Author:Sawashita J, Zhang B, Hasegawa K, Mori M, Naiki H, Kametani F, Higuchi K


A nonsense nucleotide substitution in the oculocutaneous albinism II gene underlies the original pink-eyed dilution allele (Oca2(p)) in mice
Exp Anim,64(2):171-179 2015
Author:Shoji H, Kiniwa Y, Okuyama R, Yang M, Higuchi K, Mori M


NFκB2 Gene as a Novel Candidate that Epigenetically Responds to Interval Walking Training
Int J Sports Med,36(9):769-775 2015
Author:Zhang Y, Hashimoto S, Fujii C, Hida S, Ito K, Matsumura T, Sakaizawa T, Morikawa M, Masuki S, Nose H, Higuchi K, Nakajima K, Taniguchi S


The first pure form of Ostertag-type amyloidosis in Japan: a sporadic case of hereditary fibrinogen Aα-chain amyloidosis associated with a novel frameshift variant
Amyloid,22(2):142-144 2015
Author:Yazaki M, Yoshinaga T, Sekijima Y, Nishio S, Kanizawa Y, Kametani F, Miyashita K, Hachiya N, Higuchi K, Ikeda S


AA amyloidosis-resistant CE/J mice have Saa1 and Saa2 genes that encode an identical SAA isoform
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS,21(1):1-8 2014(Mar.)
Author:Mori, M; Tiang, G; Higuchi, K


Transmission of Systemic AA Amyloidosis in Animals
VETERINARY PATHOLOGY,51(2):363-371 2014(Mar.)
Author:Murakami, T; Ishiguro, N; Higuchi, K


Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice
Antioxid Redox Signal,20(16):2606-2620 2014
Author:Tian G, Sawashita J, Kubo H, Nishio SY, Hashimoto S, Suzuki N, Yoshimura H, Tsuruoka M, Wang Y, Liu Y, Luo H, Xu Z, Mori M, Kitano M, Hosoe K, Takeda T, Usami S, Higuchi K


Diversity and complexity of the mouse Saa1 and Saa2 genes
Exp Anim,63(1):99-106 2014
Author:Mori M, Tian G, Ishikawa A, Higuchi K


Senile systemic amyloidosis (Japanese)
Brain Nerve,266(7):817-826 2014
Author:Yazaki M, Higuchi K


The toxicity mechanisms of action of Aβ25-35 in isolated rat cardiac myocytes
Molecules,19(8):12242-12257 2014
Author:Zhang B, Bian X, He P, Fu X, Higuchi K, Yang X, Li D


Novel frame-shift mutation in Slc5a2 encoding SGLT2 in a strain of senescence-accelerated mouse SAMP10
Biochem Biophys Res Commun,454(1):89-94 2014
Author:Unno K, Yamamoto H, Toda M, Hagiwara S, Iguchi K, Hoshino M, Takabayashi F, Hasegawa-Ishii S, Shimada A, Hosokawa M, Higuchi K, Mori M


Hereditary cataract of the Nakano mouse: Involvement of a hypomorphic mutation in the coproporphyrinogen oxidase gene
EXPERIMENTAL EYE RESEARCH,112:45-50 2013(Jul.)
Author:Mori, M; Gotoh, S; Taketani, S; Hiai, H; Higuchi, K


Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes
BMC GENOMICS,14:248 2013
Author:Tanisawa, K; Mikami, E; Fuku, N; Honda, Y; Honda, S; Ohsawa, I; Ito, M; Endo, S; Ihara, K; Ohno, K; Kishimoto, Y; Ishigami, A; Maruyama, N; Sawabe, M; Iseki, H; Okazaki, Y; Hasegawa-Ishii, S; Takei, S; Shimada, A; Hosokawa, M; Mori, M; Higuchi, K; Takeda, T; Higuchi, M; Tanaka, M


An interleukin-33 gene polymorphism is a modifier for eosinophilia in rats
GENES AND IMMUNITY,14(3):192-197 2013
Author:Luo, H; Higuchi, K; Matsumoto, K; Mori, M


Genes for Difference in Eosinophilic Phenotype between MES and BN.MES-Cyba(mes) Rats Are on Chromosomes 9, 5, and 1
EXPERIMENTAL ANIMALS,60(2):151-160 2011(Apr.)
Author:Tomozawa, Hiroshi; Nishio, Ayako; Higuchi, Keiichi; Matsumoto, Kiyoshi; Mori, Masayuki


Exercise Effects on Methylation of ASC Gene
INTERNATIONAL JOURNAL OF SPORTS MEDICINE,31(9):671-675 2010(Sep.)
Author:Nakajima, K.; Takeoka, M.; Mori, M.; Hashimoto, S.; Sakurai, A.; Nose, H.; Higuchi, K.; Itano, N.; Shiohara, M.; Oh, T.; Taniguchi, S.


BN.MES-Cyba(mes) Congenic Rats Manifest Focal Necrosis with Eosinophilic Infiltration in the Liver without Blood Eosinophilia
EXPERIMENTAL ANIMALS,59(4):469-478 2010(Jul.)
Author:Tomozawa, Hiroshi; Nishio, Ayako; Okuhara, Yuji;Higuchi, Keiichi; Matsumoto, Kiyoshi; Mori, Masayuki


Mouse model to study human A beta M-2 amyloidosis: generation of a transgenic mouse with excessive expression of human beta(2)-microglobulin
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS,17(2):50-62 2010(Jun.)
Author:Zhang, Pengyao; Fu, Xiaoying; Sawashita, Jinko; Yao, Junjie; Zhang, Beiru; Qian, Jinze; Tomozawa, Hiroshi; Mori, Masayuki; Ando, Yukio; Naiki, Hironobu; Higuchi, Keiichi


Mouse Senile Amyloid Fibrils Deposited in Skeletal Muscle Exhibit Amyloidosis-Enhancing Activity
PLOS PATHOGENS,6(5):e1000914 2010(May)
Author:Qian, Jinze; Yan, Jingmin; Ge, Fengxia; Zhang, Beiru; Fu, Xiaoying; Tomozawa, Hiroshi; Sawashita, Jinko; Mori, Masayuki; Higuchi, Keiichi


Genetic basis of inter-individual variability in the effects of exercise on the alleviation of lifestyle-related diseases
JOURNAL OF PHYSIOLOGY-LONDON,587(23):5577-5584 2009(Dec.)
Author:Mori, Masayuki; Higuchi, Keiichi; Sakurai, Akihiro; Tabara, Yasuharu; Miki, Tetsuro; Nose, Hiroshi


Amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,1794(10):1517-1529 2009(Oct.)
Author:Sawashita, Jinko; Kametani, Fuyuki; Hasegawa, Kazuhiro; Tsutsumi-Yasuhara, Shinobu; Zhang, Beiru; Yan, Jingmin; Mori, Masayuki; Naiki, Hironobu; Higuchi, Keiichi


Effects of mild calorie restriction and high-intensity interval walking in middle-aged and older overweight Japanese
EXPERIMENTAL GERONTOLOGY,44(10):666-675 2009(Oct.)
Author:Sawashita, Jinko; Onitsuka, Sayaka; Gen-no, Hirokazu; Ishikawa, Shinobu; Iino, Fumie; Tateishi, Norihiko; Murakami, Takeo; Seki, Yoichi; Nagaiwa, Toshiyuki; Hanaoka, Masaaki; Hama, Sumio; Nose, Hiroshi; Higuchi, Keiichi


Dysfunction in ABCB1A Has Only a Weak Effect on Susceptibility to Dextran Sulfate Sodium-Induced Colitis in SAM Strains
EXPERIMENTAL ANIMALS,58(4):421-425 2009(Jul.)
Author:Zhang, Guohong; Fu, Xiaoying; Takeda, Toshio; Higuchi, Keiichi; Mori, Masayuki


Hereditary Pancreatitis Model WBN/Kob Rat Strain Has a Unique Haplotype in the Pdwk1 Region on Chromosome 7
EXPERIMENTAL ANIMALS,58(4):409-413 2009(Jul.)
Author:Mori, Masayuki; Fu, Xiaoying; Chen, Lei; Zhang, Guohong; Higuchi, Keiichi


Apolipoprotein A-II accelerates reactive AA amyloidosis.
Amyloid,24(sup1):147-148 2007(May)
Author:Yang M, Liu Y, Li L, Miyahara H, Ding X, Dai J, Sawashita J, Mori M, Higuchi K.
Keywords:Amyloid


Diurnal rhythm disorder of behavioral activity in SAMP1 mice is partially normalized by spontaneous wheel running.
PHYSIOLOGY&BEHAVIOR,80(2-3):195-201 2003
Author:Yanagidaira, Y; Higuchi, K; Nose, H


Spontaneous hypomorphic mutations in antioxidant enzymes of mice (2003)
Free Radic Biol Med. 2003
Author:Guo Z, Higuchi K, Mori M.


Amyloidosis modifier genes in less amyloidogenic A/J mouse strain.
Lab Invest 2003
Author:Guo Z, Mori M, Fu X, Yao J, Xing Y, Korenaga T, Li G, Matsushita T, Hosokawa M, Higuchi K.


Dietary fat modulation of apoA-II metabolism and prevention of senile amyloidosis in the senescence- accelerated mouse.
J Lipid Res.,44(4):762-769 2003
Author:Umezawa M, Tatematsu K, Korenaga T, Fu X, Matushita T, Okuyama H, Hosokawa M, Takeda T, Higuchi K.


Amyloid Fibril Proteins.
Mech Ageing Dev.,123(12):1625-1636 2002
Author:Xing Y, Higuchi K


Induction of protein conformational change in mouse senile amyloidosis.
J Biol Chem.,277(36):33164-33169 2002
Author:Xing Y, Nakamura A, Korenaga T, Guo Z, Yao J, Fu X, Matsushita T, Kogishi K, Hosokawa M, Kametani F, Mori M, Higuchi K. (2002).


Spontaneous Loss-of-Function Mutations of the 8-Oxoguanine DNA Glycosylase Gene in Mice and Exploration of the Possible Implication of the Gene in Senescence
Free Rad. Biol. Med,30:1130-1136 2001
Author:M. Mori, S. Toyokuni, S. Kondo合計7名


Extra-Hepatic Expression of Apolipoprotein A-II mRNA Revealed by In Situ Hybridization Analysis; Possible Contribution to Mouse Senile Amyloidosis
J. Histochem. Cytochem,49:739-748 2001
Author:L. Fu, I. Matuyama, T. Chiba 他6名


老化促進マウス(SAM)の解析
BIO Clinica,16:57-61 2001
Author:樋口京一、森 政之


Chromosome 13Locus, Pbd2, Regulates Bone Density in Mice
J. Bone Miner. Res,16:1972–1982 2001
Author:M. Shimizu, K. Higuchi, M. Matsushita 他5名


Transmission of Mouse Senile Amyloidosis
Lab. Invest,81:493-499 2001
Author:Y. Xing, A. Nakamura, T. Chiba 他2名


Wild type ApoA-II gene does not rescue senescence-accelerated mouse (SAMP1) from short life span and accelerated mortality
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES,55(9):B432-B439 2000
Author:Wang, J; Matsushita, T; Kogishi, K; Xia, C; Ohta, A; Chiba, T; Nakamura, A; Kondo, H; Mori, M; Hosokawa, M; Higuchi, K


Genetic Analysis of Lifespan in Hybrid Progeny Derived From the SAMP1 Mouse Strain with Accelerated Senescence
Mech. Ageing Dev.,118:35-44 2000
Author:Z. Guo, E. Toichi, M. Hosono 他4 名


Senescence-Accelerated Mouse
Methods Enzymol,309:674-686 1999
Author:K. Higuchi, M. Hosokawa, T. Takeda.


Mouse Senile Amyloid Deposition Is Suppressed by Adenovirus-Mediated Overexpression of Amyloid-Resistant Apolipoprotein A-II
Am. J. Pathol.,155:1319-1326 1999
Author:T. Chiba, K. Kogishi, J. Wang 他7名

研究費
受託研究
CoQの抗老化効果

科学研究費補助金(研究代表者)
2017 - 2019 , アミロイドーシスの統合病理学:伝播現象の把握から新たな治療法を探る , 基盤研究(B)
2017 - 2019 , 還元型コエンザイム Q10の寿命延長効果の検証 , 挑戦的研究(萌芽)

受託事業
2003 - , アミロイドーシスに関する調査研究 (厚生労働省)

教育活動実績

授業等
2002 , 加齢生物学
2002 , 実験病理学