最近の研究業績

【論文および総説】

2020

Roles of Gangliosides in Hypothalamic Control of Energy Balance: New Insights. Kei-ichiro Inamori and Jin-ichi Inokuchi (2020)International journal of molecular sciences

DOI: 10.3390/ijms21155349

Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity. 

Hirotaka Kanoh, Takahiro Nitta, Shinji Go, Kei-Ichiro Inamori, Lucas Veillon, Wataru Nihei, Mayu Fujii, Kazuya Kabayama, Atsushi Shimoyama, Koichi Fukase, Umeharu Ohto, Toshiyuki Shimizu, Taku Watanabe, Hiroki Shindo, Sorama Aoki, Kenichi Sato, Mika Nagasaki, Yutaka Yatomi, Naoko Komura, Hiromune Ando, Hideharu Ishida, Makoto Kiso, Yoshihiro Natori, Yuichi Yoshimura, Asia Zonca, Anna Cattaneo, Marilena Letizia, Maria Ciampa, Laura Mauri, Alessandro Prinetti, Sandro Sonnino, Akemi Suzuki, Jin-Ichi Inokuchi

The EMBO journal e101732 2020年5月7日 

The ceramide analogue N-(1-hydroxy-3-morpholino-1-phenylpropan-2-yl)decanamide induces large lipid droplet accumulation and highlights the effect of LAMP-2 deficiency on lipid droplet degradation. 

Yuji Kato, Satoko Arakawa, Kazue Terasawa, Jin-Ichi Inokuchi, Takanori Iwata, Shigeomi Shimizu, Tetsuro Watabe, Miki Hara-Yokoyama

Bioorganic & medicinal chemistry letters 30 (3)(126891) 1 - 6 2020年2月1日 


2019

Overexpression of HexCer and LacCer containing 2-hydroxylated fatty acids in cholangiocarcinoma and the association of the increase of LacCer (d18:1-h23:0) with shorter survival of the patients. Glycoconj. J 36, 103-111 (2019)

Silsirivanit A, Phoomak C, Teeravirot K, Wattanavises S, Seubwai W, Saengboonmee C, Zhan Z, Inokuchi J, Suzuki A, Wongkham S.

https://doi.org/10.1007/s10719-019-09864-4


Visual Function in Mice Lacking GM3 Synthase. Curr. Eye Res. (2019) DOI: 10.1080/02713683.2019.1576206

Hiraoka M, Ohkawa E,Abe A, Murata M, Go S, Inokuchi J and Ohguro H.


Serum GM3(d18:1-16:0) and GM3(d18:1-24:1) levels may be associated with lymphoma: An exploratory study with haematological diseases. Sci. Rep. 9:6308, (2019) | https://doi.org/10.1038/s41598-019-42817-3

Nishikawa M, Kurano M, Nitta T, Kanoh H, Inouchi J and Yatomi Y.


Plasma membrane sphingomyelin modulates thymocyte development by inhibiting TCR-induced apoptosis. International Immunology 31, 211-223. (2019) doi:10.1093/intimm/dxy082

Toshima K, Nagafuku M, Okazaki T, Kobayashi T, Inokuchi J.


Globo-series glycosphingolipids enhance lipopolysaccharide-induced inflammation and play a pathophysiological role in diabetic nephropathy. Glycobiology 29, 260-268. (2019)  doi: 10.1093/glycob/cwy105

Nitta T, Kanoh H, Inamori K, Suzuki A, Takahashi T, and Inokuchi J.


2018

Biology of GM3 ganglioside (Book Chapter in Gangliosides in Health and Diseases).  Inokuchi J, Inamori K, Kabayama K, Nagafuku M, Uemura S, Go S, Suzuki A, Ohno I, Kanoh H, Shishido F. Progress in Molecular Biology and Translational Science (Schnaar RL., Lopez PHH., eds, Elsevior) page152-195 ISBN978-0-12-81234-6 (https://doi.org/10.1016/bs.pmbts.2017.10.004) (2018).


Deficient Overexpression of HexCer and LacCer containing 2-

hydroxylated fatty acids in cholangiocarcinoma and the association of the increase of LacCer

(d18:1-h23:0) with shorter survival of the patientsganglioside synthesis restores responsiveness to leptin and melanocortin signaling in obese KKAy mice. Inamori K, Ito H, Tamura Y, Nitta T,Yang X, Nihei W, Shishido F, Imazu S, Tsukita S, Yamada T. Katagiri H, Inokuchi J. (2018)  J Lipid Res. 59, 1472-1481.


NPC1L1-dependent intestinal cholesterol absorption requires ganglioside GM3 in membrane microdomains. J Lipid Res. 59, 2181-2187Nihei W, Nagafuku M, Hayamizu H, Odagiri Y, Tamura Y, Kikuchi Y, Veillon L, Kanoh H, Inamori K, Arai K, Kabayama K, Fukase K, Inokuchi J.



Plasma membrane sphingomyelin modulates thymocyte development by inhibiting TCR-induced apoptosis. Toshima K, Nagafuku M, Okazaki T, Kobayashi T, Inokuchi J.  International Immunology doi:10.1093/intimm/dxy082, 2018.


The regulatory roles of glycosphingolipid-enriched lipid rafts in immune systems. Nakayama H, Nagafuku M, Akemi Suzuki A, Iwabuchi K. and Inokuchi J.  FEBS letters doi:10.1002/1873-3468.13275, 2018.


Globo-series glycosphingolipids enhance lipopolysaccharide-induced inflammation and play a pathophysiological role in diabetic nephropathy. Nitta T, Kanoh H, Inamori K, Suzuki A, Takahashi T, and Inokuchi J.  Glycobiology 29, 260-268, 2019.


Visual function in mice lacking GM3 synthase. Hiraoka M, Ohkawa E, Abe A, Murata M, Go S, Inokuchi J and Ohguro H. Curr. Eye Res. https://doi.org/10.1080/02713683.2019.1576206


2017

Gangliosides and Hearing. Inokuchi J, Go S, Yoshikawa M, Straus KA. (2017)

Biochim. Biophys. Acta 1861;2485-2493.


Identification of a new liver-specific c-type mRNA transcriptional variant for mouse ST3GAL5 (GM3/GM4 synthase).Shishido F, Uemura S, Nitta T, Inokuchi J. (2017)

Glycoconj. J; DOI 10.1007/s10719-017-9788-1


Identification of a new B4GalNAcT1 (GM2/GD2/GA2 synthase) isoform, and regulation of enzyme stability and intracellular transport by arginine-based motif. Shishido F, Uemura S, Kashimura M,

Inokuchi J. (2017) Biochim. Biophys. Acta 1859;2001-2011.


Altered expression of ganglioside GM3 molecular species and a potential regulatory role during myoblast differentiation. Go S, Go SVeillon LCiampa MGMauri LSato CKitajima K,Prinetti A, Sonnino S, Inokuchi J.  (2017)

J Biol Chem. 292, 7040-7051.


PDMP, a ceramide analogue, acts as an inhibitor of mTORC1 by inducing its translocation from lysosome to endoplasmic reticulum.Ode T, Podyma-Inoue KA, Terasawa K, Inokuchi J, Kobayashi T, Watabe T, Izumi Y, Hara-Yokoyama M (2017) Exp. Cell Res. 350:103-114.



2016

Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow. Watanabe H, Okahara K, Naito-Matsui Y, Abe M, Go S, Inokuchi J, Okazaki T, Kobayashi T, Kozutsumi Y, Oka S, Takematsu H. (2016)

Mol Biol Cell. 27:2037-2050.


Targeting CERS6-dependent Metastasis-prone Phenotype in Lung Cancer Cells.Suzuki M, Cao K, Kato S, Komizu Y, Tanaka K, Togawa N, Arima C, Chee T-M, Yanagisawa K, Usami N, Taniguchi T, Yokoi K, Mizutani Y, Igarashi Y, Inokuchi J, Iwaki S, Fujii S, Ueoka R, Tamiya-Koizumi K, Murate T, Kyogashima M, Nakamura M, and Takahashi T. (2016)

J. Clin. Invest. 126:254-265.


2015

Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome

Veillon L, Go S, Matsuyama W, Suzuki A, Nagasaki M, Yatomi Y, Inokuchi J. (2015) PLOS ONE

DOI: 10.1371/journal.pone.0129645


Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells.

Yoshikawa M, Go S, Suzuki S, Suzuki A, Morlet T, Strauss K, Fujiwara M, Iwasaki K,

   and Inokuchi J. (2015) Hum Mol. Genet. 24: 2796-2807


Control of homeostatic and pathogenic balance in adipose tissue by ganglioside GM3.

Nagafuku M, Sato T, Sato S, Shimizu K, Taira T, and Inokuchi J. (2015)

Glycobiology 25: 303-318


Distinct Selectivity of Gangliosides Required for CD4+ T and CD8+ T Cell Activation.

Inokuchi J, Nagafuku M, Ohno I, and Suzuki A. (2015)

Biochim. Biophys. Acta 185: 98-106


2014

GM3 and Diabetes.

Inokuchi J. (2014)

Glycoconj. J. 31: 193-197


Loss of hydroxyl groups from the ceramide moiety can modify the lateral diffusion of membrane proteins in Saccharomyces cerevisiae.

Uemura S, Shisido F, Tani M, Mochizuki T, Abe F, and Inokuchi J. (2014)

J. Lipid Res. 55:1343-1356,


Functional mapping and implications of substrate specificity of the yeast high-affinity leucine

permease Bap2.

Usami Y, Uemura S, Michizuki T, Morita A, Sfisido F, Inokuchi J, and Abe F. (2014)

Biochim. Biophys. Acta 1838:1719-1729



Expression machinery of GM4: the excess amounts of GM3/GM4S synthase (ST3GAL5) are necessary for GM4 synthesis in mammalian cells.

Uemura S, Go S, Shishido F, Inokuchi J. (2014)

Glycoconj. J. 31:101–108



2013

The Physiological Significance of Ganglioside Species Selectively Expressed on Individual T Cell Subsets.

Nagafuku M, Inokuchi J, (2013)

Trends in Glycoscience and Glycotechnology 25: 159-169


Heterogeneity of gangliosides among T cell subsets

Inokuchi J., Nagafuku M., Ohno I. and Suzuki A. (2013)

Cell. Mol. Life Sci. 70: 3067-3075


Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody.

Hayashi N, Chiba H, Kuronuma K, Go S, Hasegawa Y, Takahashi M, Gasa S, Watanabe A,

Hasegawa T, Kuroki Y, Inokuchi J and  Takahashi H. (2013)

Cancer Sci. 104: 43-47



2012

Impairment of hippocampal long-term potentiation and failure of learning in mice treated with D-threo-1phenyldecanoylamino-1-propanol. 

Fujiwara M,Ikarashi K, Yamazaki Y, Goto J, Kaneko K, Sugita M, Kato H, Sasaki H, Inokuchi J, Furukawa K, and Fujii S. (2012)

Biomedical Res. 33: 265-271.


CD4 and CD8 T cells require different membrane gangliosides for activation. 

Nagafuku M, Okuyama K., Onimaru Y., Suzuki A., Odagiri Y., Yamashita T., Iwasaki K., Fujiwara M., Takayanagi M., Ohno I. and Inokuchi J. (2012)

Proc. Natl. Acad. Sci.USA 109: E336-E342


Dissociation of the insulin receptor from caveolae during TNFa-induced insulin resistance and its recovery by D-PDMP.

Sekimoto J., Kabayama K., Gohara K., and Inokuchi J. (2012)

FEBS Lett. 586: 191-195



2011


CD4+T細胞とCD8+T細胞の活性化におけるラフトガングリオシドの相違

永福正和、井ノ口仁一 (2011)

臨床免疫・アレルギー科 55: 460-469


“Physiopathological function of hematoside (GM3 ganglioside)”

Inokuchi, J. (2011)

Proc. Jpn. Acad., Ser. B. 87: 179-198


Glycoconjugates in the mammalian auditory system.

Go S, Yoshikawa M, Inokuchi J. (2011)

J. Neurochem. 116: 756-763



糖鎖によるアレルギー性免疫応答の調節

奥山香織、大野勳、永福正和、井ノ口仁一(2011)

呼吸 30: 223-229


聴覚機能における複合糖質の役割

郷慎司、吉川弥里、井ノ口仁一 (2011)

生化学  3:179-188



2010


Membrane Microdomains and Insulin Resistance.

Inokuchi J. (2010)

FEBS letters 584: 1864-1871


聴覚におけるガングリオシドの機能

郷 慎司、吉川 弥里、井ノ口 仁一 (2010)

化学と生物 Vol.48, No.11, 736-738


糖鎖と難聴

郷 慎司、吉川 弥里、井ノ口 仁一 (2010)

生体の科学(金原一郎記念医学医療振興財団刊)、Vol.61(2), 135-141



2009


Specific expression of Neu2 type B in mouse thymus and the existence of a membrane-bound form in COS cells.

Koda T, Kijimoto-Ochiai S, Uemura S, Inokuchi J. (2009)

Biochem Biophys Res Commun. 387(4), 729-35.


Zebrafish and mouse alpha2,3-sialyltransferases responsible for synthesizing GM4 ganglioside.

Chisada S, Yoshimura Y, Sakaguchi K, Uemura S, Go S, Ikeda K, Uchima H, Matsunaga N, Ogura K, Tai T, Okino N, Taguchi R, Inokuchi J, Ito M. (2009)

J. Biol. Chem. 284(44), 30534-46.


The Cytoplasmic tail of GM3 synthase defines its subcelluar localization, stability, and in vivo activity.

Uemura S., Yoshida S., Shishido F., and Inokuchi J. (2009)

Mol. Biol. Cell 20: 3088-3100


Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to    selective degeneration of the organ of Corti.

Yoshikawa M., Go S., Takasaki K., Kakazu Y., Ohashi M., Nagafuku M., Kabayama K., Sekimoto J., Suzuki S., Takaiwa K., Kimitsuki T., Matsumoto N., Komune S., Kamei D., Saito M., Fujiwara M., Iwasaki K. and Inokuchi J. (2009)

Proc. Natl. Acad. Sci.USA 106: 9483-9488


Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging.

Tajima O., Egashira N., Ohmi Y., Fukue Y., Mishima K., Iwasaki K., Fujiwara M., Inokuchi J., Sugiura Y. and Furukawa K. (2009)

Behav. Brain Res. 198: 74-82.


Neurotrophic and Neuroprotective Actions of an Enhancer of Ganglioside Biosynthesis. In G. Bagetta, M.T. Corasaniti, T. Sakurada, S. Sakurada,

Inokuchi J. (2009)

International Review of Neurobiology, 85: 319-336.

Burlington: Academic Press


腸間膜脂肪細胞の生理的分化成熟法の確立

佐藤貴繁、永福正和、清水恭子、水口孝大、井ノ口仁一  (2009)

組織培養研究、Vol. 28, 145-157


2008


Physiological levels of insulin and IGF-1 synergistically enhance the differentiation of mesenteric adipocytes.

Sato T., Nagafuku M., Shimizu K., Taira T., Igarashi Y. and Inokuchi J. (2008)

Cell Biol. Int. 32: 1397-1404


Circulating Levels of Ganglioside GM3 in Metabolic Syndrome: A Pilot Study.

Sato T., Nihei Y., Nagafuku M., Tagami S., Chin R., Kawamura M., Miyazaki S., Suzuki M., Sugahara S., Takahashi Y., Saito A., Igarashi Y. and Inokuchi J. (2008)

Obesity Research & Clinical Practice 2: 231-238


Modulation of Growth Factor Receptors in Membrane Microdomains

Inokuchi J. and Kabayama K. (2008)

Trends in Glycoscience and Glycotechnology 20: 353-371



2007



Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance.

Kabayama K., Sato T., Saito K., Loberto N., Prinetti A., Sonnino S., Kinjo M., Igarashi Y. and Inokuchi J. (2007)

Proc. Natl. Acad. Sci.USA, 104: 13678-13683


GM3 synthase gene is a novel biomarker for histological classification and drug sensitivity against epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.

Noguchi M., Suzuki T., Kabayama K., Takahashi H., Chiba H., Shiratori M., Abe S., Watanabe A., Satoh M., Hasegawa T., Tagami S., Ishii A., Saito M., Kaneko M., Iseki K., Igarashi Y. and Inokuchi J. (2007)

Cancer Science 98: 1625-1632


Cell Growth Arrest by Sialic Acid Clusters in Ganglioside GM3 Mimetic Polymers.

Uemura S., Fei Feng, Kume M., Yamada K., Kabayama K., Nishimura S., Igarashi Y. and Inokuchi J. (2007)

Glycobiology 17: 568-577


Regulation of the transport and protein levels of the inositol phosphorylceramide mannosyltransferases Csg1 and Csh1 by the Ca2+ -binding protein Csg2.

Uemura S., Kihara A., Iwaki S., Inokuchi J. and Igarashi Y. (2007)

J. Biol. Chem. 282: 8613-8621



【著書】


Sugar Chains (Macrophages govern ganglioside GM3 expression in adipocytes to regulate

adipogenesis and insulin signaling in homeostatic and pathogenic conditions)

Inokuchi J.

Springer Japan 2015


Sugar Chains (Gangliosides and T cell immunity)

Nagafuku M, and Inokuchi J. Springer Japan

2015


Glycobiology of the Nervous System, Advances in Neurobiology 9 (Synthesis of O-Linked

Glycoconjugates in the Nervous System.)

Inokuchi J. Go S. and Hirabayashi Y. Springer Science+Business Media New York. Chapter 4, DOI 10.1007/978-1-4939-1154-7_4, 2014


Handbook of Glycosyltransferases and Related Genes. Second Edition.

(ST3 beta-galactoside alpha-2,3-sialyltransferase 5;ST3GAL5)

Inokuchi J. and Uemura S. Springer Japan 2014


Handbook of Glycosyltransferases and Related Genes. Second Edition. (Biosynthetic Pathways of Glycosphingolipids) Inokuchi J. and Go S. Springer Japan 2014


Inhibition of ganglioside biosynthesis as a novel therapeutic approach in insulin resistance.

Inokuchi J. (2011)

Handbook of Experimental Pharmacology 203,165-78(Springer)


インスリンの効き方は糖鎖が決めている「第3の生命鎖:糖鎖の謎が今、解る

井ノ口仁一 (2009)  

P232-237(クバプロ)


Insulin Resistance and Type 2 Diabetes as Microdomain Disease: Implication of Ganglioside GM3.

Inokuchi J. and Kabayama K. (2008)

Experimental Glycoscience (Glycobiology) 333-336 (Springer)


Modulation of Growth Factor Receptors in Membrane Microdomains

Inokuchi J. and Kabayama K. (2008)

Trends in Glycoscience and Glycotechnology 20, 353-371


ミクロドメインにおけるインスリン受容体の機能調節「糖鎖情報の独自性と普遍性」

井ノ口仁一、樺山一哉、永福正和、佐藤貴繁 (2008)

蛋白質核酸酵素 9月号増刊 Vol.53 No.12,1552-1557


ガングリオシドが関与する新たなインスリン抵抗性のメカニズム

井ノ口仁一、樺山一哉、永福正和、佐藤貴繁 (2008)

Medical Bio 5月号76-81(オーム社)


マイクロドメイン異常症としてのインスリン抵抗性

樺山一哉、井ノ口仁一 (2008)

THE LUNG 16: 82-88 (メディカルビュー社)