具体的な研究テーマ

1. タンパク質の糖付加修飾C-／N-マンノシル化の細胞生物機能の解明
2. ERシャペロン・カルレティキュリンの生理機能とEMTにおける役割の解明
3. タンパク質のレドックス「酸化還元」制御による細胞シグナル伝達機構の解明

［英語原著論文と総説］

2022

Takeda-Uchimura Y, Nishitsuji K, Ikezaki M, Akama TO, Ihara Y, Allain F, Uchimura K. Beta3Gn-T7 Is a Keratan Sulfate β1,3 N-Acetylglucosaminyltransferase in the Adult Brain. Front Neuroanat., 16, 813841, 2022.

Ikezaki M, Nishitsuji K, Matsumura K, Manabe S, Shibukawa Y, Wada Y, Ito Y, Ihara Y. C-Mannosylated tryptophan-containing WSPW peptide binds to actinin-4 and alters E-cadherin subcellular localization in lung epithelial-like A549 cells. Biochimie., 192, 136-146, 2022.

2021

Nishitsuji K, Ikezaki M, Manabe S, Uchimura K, Ito Y, Ihara Y. Thrombospondin type 1 repeat-derived C-mannosylated peptide attenuates synaptogenesis of cortical neurons induced by primary astrocytes via TGF-β. Glycoconj J., 2021.

Iwahashi N, Ikezaki M, Fujimoto M, Komohara Y, Fujiwara Y, Yamamoto M, Mizoguchi M, Matsubara K, Watanabe Y, Matsuzaki I, Murata SI, Ihara Y, Ino K, Nishitsuji K. Lipid Droplet Accumulation Independently Predicts Poor Clinical Prognosis in High-Grade Serous Ovarian Carcinoma. Cancers (Basel)., 13, 5251, 2021.

Minakata S, Manabe S, Inai Y, Ikezaki M, Nishitsuji K, Ito Y, Ihara Y. Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine. Molecules., 26, 5258, 2021.

Iwahashi N, Ikezaki M, Nishitsuji K, Yamamoto M, Matsuzaki I, Kato N, Takaoka N, Taniguchi M, Murata SI, Ino K, Ihara Y. Extracellularly Released Calreticulin Induced by Endoplasmic Reticulum Stress Impairs Syncytialization of Cytotrophoblast Model BeWo Cells. Cells., 10, 1305, 2021.

Morita S, Inai Y, Minakata S, Kishimoto S, Manabe S, Iwahashi N, Ino K, Ito Y, Akamizu T, Ihara Y. Quantification of serum C-mannosyl tryptophan by novel assay to evaluate renal function and vascular complications in patients with type 2 diabetes. Sci Rep., 11, 1946, 2021.

Iwahashi N, Ikezaki M, Saito H, Uchimura K, Nishitsuji K. Cell-to-cell transmission of p53 aggregates: a novel player in oncology? Mol Cell Oncol., 8, 1892444, 2021.

Ohgita T, Furutani Y, Nakano M, Hattori M, Suzuki A, Nakagawa M, Naniwa S, Morita I, Oyama H, Nishitsuji K, Kobayashi N, Saito H, Novel conformation‐selective monoclonal antibodies against apoA‐I amyloid fibrils, FEBS J., 288, 1496-1513, 2021.

2020

Iwahashi N, Ikezaki M, Nishikawa T, Namba N, Ohgita T, Saito H, Ihara Y, Shimanouchi T, Ino K, Uchimura K, Nishitsuji K, Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates. Proc Natl Acad Sci U S A., 117, 33225-33234, 2020.

Minakata S, Inai Y, Manabe S, Nishitsuji K, Ito Y, Ihara Y, Monomeric C-mannosyl tryptophan is a degradation product of autophagy in cultured cells. Glycoconj J. 37, 635-645, 2020.

Ohgita T, Takechi-Haraya Y, Okada K, Matsui S, Takeuchi M, Saito C, Nishitsuji K, Uchimura K, Kawano R, Hasegawa K, Sakai-Kato K, Akaji K, Izutsu KI, Saito H, Enhancement of direct membrane penetration of arginine-rich peptides by polyproline II helix structure. Biochim Biophys Acta Biomembr., 1862, 183403, 2020.

Inai Y, Ueda K, Matsui IL, Tajiri M, Minakata S, Wada Y, Ihara Y, Role of C-mannosylation in the secretion of mindin. Biochim Biophys Acta Gen Subj., 1864, 129632, 2020.

Ikezaki M, Nishioka N, Nishikawa T, Higashimoto N, Ihara Y. Hsc70 is required for E-cadherin expression in epithelial-like NRK-52E cells. Biochem Biophys Res Commun., 527, 481-488, 2020.

Ihara Y, Ikezaki M, Takatani M, Ito Y, Calnexin/Calreticulin and Assays Related to N-Glycoprotein Folding In Vitro. Methods Mol Biol., 2132, 295-308, 2020.

Ikezaki M, Minakata S, Nishitsuji K, Tabata S, Lee Matsui IS, Takatani M, Usukura J, Ito Y, Ihara Y, Calreticulin protects insulin against reductive stress in vitro and in MIN6 cells. Biochimie., 171-172, 1-11, 2020.

Iwahashi N, Inai Y, Minakata S, Sakurai S, Manabe S, Ito Y, Ino K, Ihara Y, C-Mannosyl tryptophan increases in the plasma of patients with ovarian cancer. Oncol Lett., 19, 908-916, 2020.

2019

Sakurai S, Inai Y, Minakata S, Manabe S, Ito Y, Ihara Y, A novel assay for detection and quantification of C-mannosyl tryptophan in normal or diabetic mice. Sci Rep., 9, 4675, 2019.

Iwahashi N, Ikezaki M, Matsuzaki I, Yamamoto M, Toujima S, Murata SI, Ihara Y, Ino K, Calreticulin regulates syncytialization through control of the synthesis and transportation of E-cadherin in BeWo cells. Endocrinology., 160, 359-374, 2019.

2017

Yamamoto M, Ikezaki M, Toujima S, Iwahashi N, Mizoguchi M, Nanjo S, Minami S, Ihara Y, Ino K, Calreticulin Is Involved in Invasion of Human Extravillous Trophoblasts Through Functional Regulation of Integrinβ1.  Endocrinology., 158, 3874-3889, 2017.

2016

Ikezaki M, Higashimoto N, Matsumura K, Ihara Y, Hsc70 facilitates TGF-β-induced activation of Smad2/3 in fibroblastic NRK-49F cells.  Biochem. Biophys. Res. Commun., 477, 448-453, 2016.

2015

Ihara Y, Inai Y, Ikezaki M, Matsui I.-L, Manabe S, and Ito Y, C-Mannosylation: a modification on tryptophan in cellular proteins.  In “Glycoscience: Biology and Medicine” (Eds.) Taniguchi N., Endo T., Hart G.W., Seeberger P., and Wong C.-H., Springer-Verlag GmbH, Heidelberg, Germany, 1091-1099, 2015.

2013

Prakoura N., Politis PK., Ihara Y., Michalak M., Aristidis S., Charonis AS.: Epithelial calreticulin up-regulation promotes profibrotic responses and tubulointerstitial fibrosis development. Am. J. Pathol, 183, 1474-1487, 2013.

2012

Takahashi M., Miyata S., Fujii J,. Inai Y., Ueyama S., Araki M., Soga T., Fujinawa R., Nishitani C., Ariki S., Shimizu T., Abe T., Ihara Y., Nishikimi M., Kozutsumi Y., Taniguchi N., Kuroki Y.: In vivo role of aldehyde reductase. Biochim. Biophys. Acta, 1820, 1787-1796, 2012.

Inadomi C., Murata H., Ihara Y., Goto S., Urata Y., Yodoi J., Kondo T., Sumikawa K.: Overexpression of glutaredoxin protects cardiomyocytes against nitric oxide-induced apoptpsis with suppressing the S-nitrosylation of proteins and nuclear translocation of GAPDH.
Biochem. Biophys. Res. Commun., 425, 656-661, 2012.

2011

Ihara Y., Inai Y., and Ikezaki M.: Alteration of integrin-dependent adhesion and signaling in EMT-like MDCK cells established through overexpression of calreticulin. J Cell Biochem., 112, 2518–2528, 2011.

Shiraishi N., Inai Y., Hirano Y., and Ihara Y.: Calreticulin inhibits prion protein PrP-(23-98) aggregation in vitro. Biosci. Biotechnol. Biochem., 75, 1625-1627, 2011.

Ihara Y., Inai Y., and Ikezaki M.: Protein C-mannosylation and its prospective functions in the cell. Trends Glycosci. Glycotechnol., 23, 1-13, 2011.

2010

Ihara Y., Manabe S., Ikezaki M., Inai Y., In-Sook Lee Matsui., Ohta Y, Muroi E., and Ito Y.: C-Mannosylated peptides derived from the thrombospondin type 1 repeat interact with Hsc70 to modulate its signaling in RAW264.7 cells. Glycobiology, 20, 1298-1310, 2010.

2009

Chularojmontri L., Ihara Y., Muroi E., Goto S., Kondo T., and Wattanapitayakul S.: Cytoprotective role of Phyllanthus urinaria L. and glutathione-S transferase Pi in doxorubicin-induced toxicity in H9c2 cells. J. Med. Assoc. Thai., 92, Suppl 3:S43-51, 2009.

Goto S., Kawakatsu M., Izumi S.I., Urata Y., Kageyama K., Ihara Y., Koji T., and Kondo T.: Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress. Free Radic. Biol. Med., 46, 1392-403, 2009.

Totani K., Ihara Y., Matsuo I., Tsujimoto T., and Ito Y.: The recognition motif of the glycoprotein-folding sensor enzyme, UDP-glc: glycoprotein glucosyltransferase. Biochemistry, 48, 2933-2940, 2009.

Shiraishi, N., Inai Y., and Ihara Y.: Proteinase K-resistant aggregates of recombinant prion protein PrP-(23-98) are toxic to cultured cells. Protein Peptide Lett., 16, 91-96, 2009.

2008

Totani K., Ihara Y., Matsuo I., and Ito Y.: Effects of macromolecular crowding on glycoprotein processing enzymes. J. Am. Chem. Soc., 130, 2101-2107, 2008.

Ihara Y.: Calreticulin. In "Encyclopedia of Cancer, 2nd Edition" (Ed) Schwab M, Springer-Verlag GmbH, Heidelberg, Germany, pp. 456-459, 2008

2007

Muroi E., Manabe S., Ikezaki M., Urata Y., Sato S., Kondo T., Ito Y., and Ihara Y.: C-Mannosylated peptides derived from the thrombospondin type 1 repeat enhance lipopolysaccharide-induced signaling in macrophage-like RAW264.7 cells. Glycobiology, 17, 1015-1028, 2007.

Nonaka K., Kume N., Urata Y., Seto S., Kono T., Honda S., Ikeda S., Muroya T., Ikeda Y., Ihara Y., Kita T., and Kondo T.: Serum levels of S-glutathionylated proteins is a risk-marker for arteriosclerosis obliterans. Circulation J., 71, 100-105, 2007.

Ito Y., Ihara Y., and Manabe S.: C-Mannosyl tryptophan (CMW): from chemistry to cell biology. In "Comprehensive Glycoscience, from Chemistry to Systems Biology" (Kamerling J.P., ed.), pp 229-248, Elsevier, Oxford, UK, 2007

2006

Shiraishi N., Utsunomiya H., and Nishikimi M.: Combination of NADPH and copper ions generates proteinase K-resistant aggregates from recombinant prion protein. J. Biol. Chem., 281, 34880-34887, 2006.

Kondo Y., Inai Y., Sato Y., Handa S., Kubo S., Shimokado K., Goto S., Nishikimi M., Maruyama N., and Ishigami A.: Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc. Natl. Acad. Sci. U.S.A., 103, 5723-5728, 2006.

Hayashida Y., Urata Y., Muroi E., Kono T., Miyata Y., Nomata K., Kanetake H., Kondo T., and Ihara Y.: Calreticulin represses E-cadherin gene expression in MDCK cells via slug. J. Biol. Chem., 281, 32469-32484, 2006.

Totani K., Ihara Y., Matsuo I., and Ito Y.: Substrate specificity analysis of endoplasmic reticulum glucosidase II using synthetic high-mannose-type glycans. J. Biol. Chem., 281, 31502-31508, 2006.

Kanda M., Ihara Y., Murata H., Urata Y., Kono T., Yodoi J., Seto S., Yano K., and Kondo T.: Glutaredoxin modulates PDGF-dependent cell signaling by regulating the redox status of low molecular weight protein tyrosine phosphatase. J. Biol. Chem., 281, 28518-28528, 2006.

Okunaga T., Urata Y., Goto S., Matsuo T., Mizota S., Tsutsumi K., Nagata I., Kondo T., and Ihara Y.: Calreticulin, a molecular chaperone in the endoplasmic reticulum, modulates radiosensitivity of human glioblastoma U251MG cells. Cancer Res., 66, 8662-8671, 2006.

Totani K., Matsuo I., Ihara Y., and Ito Y.: High-mannose-type glycan modifications of dehydrofolate reductase using glycan-methotrexate conjugates. Bioorg. Med. Chem., 14, 5220-5229, 2006.

Urata Y., Ihara Y., Murata H., Goto S., Koji T., Yodoi J., Inoue S., and Kondo T.: 17-beta-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cells. J. Biol. Chem., 281, 13092-13102, 2006.

Ihara Y., Urata Y., Goto S., and Kondo T.: Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide. Am. J. Physiol. Cell Physiol., 290, C208-221, 2006.

2005

Inai Y., Bi W., Shiraishi N., and Nishikimi M.: Enhanced oxidative stress by L-ascorbic acid within cells challenged by hydrogen peroxide. J. Nutr. Sci. Vitaminol. (Tokyo)., 51, 398-405, 2005.

Shiraishi N., Inai Y., Bi W., and Nishikimi M.: Fragmentation and dimerization of copper-loaded prion protein by copper-catalysed oxidation. Biochem. J., 387, 247-255, 2005.

Bi W., Inai Y., Shiraishi N., Maeta K., Takatsume Y., Inoue Y., Nishikimi M.: Cytosolic protein as principal copper buffer in an early response to copper by yeast cells. J. Clin. Biochem. Nutr. 36, 19-27, 2005.

Kamiya Y., Yamaguchi Y., Takahashi N., Arata Y., Kasai K.-I., Ihara Y., Matsuo I., Ito Y., Yamamoto K., and Kato K.: Sugar-binding properties of VIP36, an intracellular animal lectin operating as a cargo receptor. J. Biol. Chem., 280, 37178-37182, 2005.

Totani K., Ihara Y., Matsuo I., Koshino H., and Ito Y.: Synthetic substrates for ER protein folding sensor, UDP-glucose: glycoprotein glucosyltransferase. Angew. Chem. Int. Ed., 44, 7950-7954, 2005.

Ihara Y., Kageyama K., and Kondo T.: Overexpression of calreticulin sensitizes SERCA2a to oxidative stress. Biochem. Biopys. Res. Commun., 329, 1343-1349, 2005.

Ihara Y., Manabe S., Kanda M., Kawano H., Nakayama T., Sekine I., Kondo T., and Ito Y.: Increased expression of protein C-mannosylation in the aortic vessels of diabetic Zucker rats. Glycobiology, 15, 383-392, 2005.

[日本語総説など]

2018

井原義人: Ⅲ．細胞膜での分子修飾 膜タンパク質 「C-マンノシル化」、増大特集 タンパク質・核酸の分子修飾、生体の科学、医学書院、69巻5号、p500-501 (2018)

2011

眞鍋史乃、井原義人、伊藤幸成：化学の窓「新規タンパク質マンノシル付加修飾：合成化学からの生物学への貢献」、化学と生物 49巻 5号、p347-351 (2011)

2010

井原義人、池﨑みどり:「酸化ストレスおよびERストレス」 糖尿病性細小血管症(第2版)-発症・進展制御の最前線-、日本臨牀 68巻 増刊号9、p49-52 (2010)

2009

井原義人:「ERと酸化ストレス、病態解明に迫る 活性酸素シグナルと酸化ストレス」 癌、神経変性疾患、循環・代謝異常にかかわるレドックス制御機構と最新の技術開発(谷口直之 監、赤池孝章、鈴木敬一郎、内田浩二 編)、実験医学 増刊、羊土社、p92-96 (2009)

古澤元, 佐藤安訓, 田中康一, 井内陽子, 天野晶, 岩間水輝, 近藤嘉高, 半田節子, 村田晃, 錦見盛光, 後藤佐多良, 丸山直記, 高橋良哉, 石神昭人:「カルニチン合成系へのビタミンCの関与」Vitamins (Japan) 83 (5" 6)、p287-289 (2009)

2008

井原義人：「分泌・膜タンパク質の折りたたみ制御と病気」　和歌山医学　59巻1号、p2-8 (2008)

2007

錦見盛光：「壊血病発症動物における遺伝子異常の解析」　ビタミン81巻1号、p1-8 (2007)

2006

井内陽子、錦見盛光：「グルコノラクトナーゼ欠損による壊血病発症」　ビタミン80巻10号、p519-520 (2006)

2005

井原義人：「分子シャペロンによる糖鎖を介したタンパク質の品質管理機構」　糖鎖科学の新展開　-機能解明・次世代材料・医薬品開発に向けて-（谷口直之、伊藤幸成　編）、エヌ・ティー・エス、p92-98 (2005) 井原義人：「糖鎖を介した糖タンパク質の品質管理とシャペロン分子機構」　糖鎖と病気（谷口直之　編）、遺伝子医学MOOK　3号、メディカルドゥ、p111-117 (2005) 近藤宇史、井原義人：「グルタチオンシステム」　レドックス - ストレス防御の医学「別冊・医学のあゆみ」、医歯薬出版、p14-18 (2005)