The role of ER stress in oral inflammatory diseases

• Project/Area Number: 24390418
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: University of Miyazaki
• Principal Investigator: NISHITOH Hideki 宮崎大学, 医学部, 教授 (00332627)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: ストレス / シグナル伝達 / 蛋白質

Outline of Final Research Achievements

Mucosa of the oral cavity region is constantly exposed to physical stress, such as acid and alcohol, and chemical stress, such as heat. Our body possesses the system to response to these stresses. Among them, the role of macrophages is important and its dysfunction may lead to cancer by its exacerbation of inflammatory diseases. One of the most famous as a stress response in the cells is the endoplasmic reticulum stress. In this study, we investigated the stress response by LPS, which is one of the toxin from bacteria, in macrophages. Our study revealed that ER stress is closely related to the function of macrophage.

Research Products

• [Journal Article] GCN5 is essential for IRF-4 gene expression followed by transcriptional activation of Blimp-1 in immature B cells. (2014)
  • Author(s): Kikuchi H, Nakayama M, Kuribayashi F, Imajoh-Ohmi S, Nishitoh H, Takami Y, Nakayama T.
  • Journal Title: J Leukoc Biol Volume: 95 Issue: 3 Pages: 399-404
  • DOI: 10.1189/jlb.0413232
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The expression of Fn14 via mechanical stress-activated JNK contributes to apoptosis induction in osteoblasts. (2014)
  • Author(s): Matsui, H., Fukuno, N., Kanda, Y., Kantoh, Y., Chida, T., Nagaura, Y., Suzuki, O., Nishitoh, H., Takeda, K., Ichijo, H., Sawada, Y., Sasaki, K., Kobayashi, T. and Tamura, S.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 10 Pages: 6438-6450
  • DOI: 10.1074/jbc.m113.536300
  • Peer Reviewed / Open Access
• [Journal Article] Protein kinase Cθ gene expression is oppositely regulated by GCN5 and EBF1 in immature B cells. (2014)
  • Author(s): Kikuchi H, Nakayama M, Kuribayashi F, Imajoh-Ohmi S, Nishitoh H, Takami Y, Nakayama T
  • Journal Title: FEBS Lett Volume: 588 Issue: 9 Pages: 1739-1742
  • DOI: 10.1016/j.febslet.2014.03.025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells. (2014)
  • Author(s): Kikuchi H., Nakayama M., Kuribayashi F., Imajoh-Ohmi S., Nishitoh H., Takami Y., Nakayama T.
  • Journal Title: Gene Volume: 544 Issue: 1 Pages: 19-24
  • DOI: 10.1016/j.gene.2014.04.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SOD1 as a molecular switch for initiating the homeostatic ER stress respouse under zinc deficiency. (2013)
  • Author(s): Homma, K., Fujisawa. T., Tsuburaya, N., Yamaguchi, N., Kadowaki, H., Takeda, K., Nishitoh, H., Matsuzawa, A., Naguro, I., and Ichijo, H.
  • Journal Title: Molecular Cell Volume: 52 Issue: 1 Pages: 75-86
  • DOI: 10.1016/j.molcel.2013.08.038
  • Peer Reviewed
• [Journal Article] Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease (2013)
  • Author(s): Kadowaki, H. Nishitoh, H.
  • Journal Title: Genes Volume: 4 Issue: 3 Pages: 306-333
  • DOI: 10.3390/genes4030306
  • Peer Reviewed
• [Journal Article] Involvement of ASK1-p38 pathway in the pathogenesis of diabetes triggered by pancreatic s cell exhaustion (2013)
  • Author(s): Yamaguchi, K., Takeda, K., Kadowaki, H., Ueda, I., Namba, Y., Ouchi, Y. Nishitoh, H. and Ichijo, H.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1830 Issue: 6 Pages: 3656-3663
  • DOI: 10.1016/j.bbagen.2013.01.029
  • Peer Reviewed
• [Journal Article] ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney. (2012)
  • Author(s): Naguro I., et al.
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1285-1285
  • DOI: 10.1038/ncomms2283
  • Peer Reviewed
• [Journal Article] A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants. (2012)
  • Author(s): Fujisawa, T., Homma, K., et al.
  • Journal Title: Ann Neurol Volume: 72 Issue: 5 Pages: 739-749
  • DOI: 10.1002/ana.23668
  • Peer Reviewed
• [Journal Article] GCN5 protects vertebrate cells against UV-irradiation via controlling gene expression of DNA polymerase n. (2012)
  • Author(s): Kikuchi H., et al.
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 47 Pages: 39842-39849
  • DOI: 10.1074/jbc.m112.406389
  • Peer Reviewed
• [Journal Article] STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. (2012)
  • Author(s): Sato T., et.al.
  • Journal Title: Molecular Cell Volume: 47(1) Issue: 1 Pages: 99-110
  • DOI: 10.1016/j.molcel.2012.04.015
  • Peer Reviewed
• [Journal Article] CHOP is a multifunctional transcription factor in the ER stress response. (2012)
  • Author(s): Nishitoh H.
  • Journal Title: J. Biochem. Volume: 151 Pages: 217-219
  • Peer Reviewed
• [Presentation] Down-regulation of Fas-mediated apoptosis by plasma transglutaminase factor XIII that catalyzes fetal-specific cross-link of the Fas molecule (2014)
  • Author(s): 菊池秀彦、栗林太、三室仁美、西頭英起、大海忍
  • Organizer: 第３７回分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Protective role of Naa60, a cellular acetyltransferase, in chemically induced DNA damage (2014)
  • Author(s): Pasjan SatrimaFitrah, 西頭 英起, 高見 恭成
  • Organizer: 第３７回分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Derlin Family Proteins Control Protein Loading into the Endoplasmic Reticulum via Substrate-Specific Cotranslational Rerouting from Translocation to Degradation (2014)
  • Author(s): Hisae Kadowaki, Hideki Nishitoh
  • Organizer: EMBOカンファレンス
  • Place of Presentation: バルセロナ
  • Year and Date: 2014-10-26 – 2014-10-30
• [Presentation] 小胞体品質管理におけるDerlinの生理的意義の解析 (2014)
  • Author(s): 西頭英起
  • Organizer: 第9回小胞体ストレス研究会
  • Place of Presentation: 徳島
  • Year and Date: 2014-07-14
• [Presentation] The molecular mechanism of novel ER quality control system (2014)
  • Author(s): Kadowaki, H., Nishitoh, H.
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] "GCN5 is essential for IRF-4 gene expression followed by transcriptional activation of Blimp-1 in immature B cells " (2014)
  • Author(s): 菊池秀彦、中山雅美、栗林太、大海忍、西頭英起、高見恭成、中山建男
  • Organizer: 第８回日本エピジェネティクス研究会年会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] Derlinファミリーを介した小胞体品質管理システム (2014)
  • Author(s): 門脇寿枝, 西頭英起
  • Organizer: 平成26年度日本生化学会九州支部例会
  • Place of Presentation: 博多
  • Year and Date: 2014-05-17 – 2014-05-18
• [Presentation] Tuning of IRE1α-Mediated Protein Degradation by the Atg5-Atg12 Conjugate (2013)
  • Author(s): Hironori Kato, Hideki Nishitoh, Masanori Kitamura
  • Organizer: FASEB "From Unfolded Proteins in the ER to Disease"
  • Place of Presentation: Vermont Academy Saxtons River. USA
• [Presentation] 新規小胞体品質管理システムの分子機構解明 (2013)
  • Author(s): 西頭英起、門脇寿枝
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋 ウインクあいち
• [Presentation] 小胞体ストレス応答におけるオートファジー関連タンパク質の役割 (2013)
  • Author(s): 加藤裕紀, 西頭英起, 北村正敬
  • Organizer: 小胞体ストレス研究会
  • Place of Presentation: 金沢大学
• [Presentation] Derlinファミリーを介した小胞体品質管理システム (2013)
  • Author(s): 西頭英起
  • Organizer: 第86回日本生化学会大会 シンポジウム
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 小胞体ストレス誘導性翻訳時分解の分子機構の解明 (2013)
  • Author(s): 門脇寿枝, 一條秀憲, 西頭英起
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Tuning of IRE1α-Mediated Protein Degradation by the Atg12-Atg5 Conjugate (2013)
  • Author(s): 加藤裕紀, 西頭英起, 北村正敬
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] GCN5は未熟B細胞で免疫グロブリン重鎖遺伝子発現制御に関与する (2013)
  • Author(s): Hidehiko Kikuchi, Masami Nakayama, Futoshi Kuribayashi, Shinobu Imajoh-Ohmi, Hideki Nishitoh, Yasunari Takami, Tatsuo Nakayama
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] S0D1-Derlin-1結合を介した小胞体ストレスの生理的・病理的意義 (2012)
  • Author(s): 西頭英起
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-12-12
• [Presentation] S0D1の構造変化により惹起される小胞体ストレスの生理的・病理的意義 (2012)
  • Author(s): 西頭英起
  • Organizer: 第36回蛋白質と酵素の構造と機能に関する九州シンポジウム
  • Place of Presentation: 宮崎市
  • Year and Date: 2012-09-06
• [Presentation] 新規小胞体品質管理システムの分子機構の解明 (2012)
  • Author(s): 西頭英起
  • Organizer: 第7回小胞体ストレス研究会
  • Place of Presentation: 広島市
  • Year and Date: 2012-09-06
• [Presentation] Molecular mechanism of novel ER quality control system (2012)
  • Author(s): Kadowaki, H., Nishitoh, H.
  • Organizer: EMBO Conference, The Physiology of the endoplasmic reticulum : FUNCTION & DYSFUNCTION
  • Place of Presentation: Caldes de Malavella, Spain
• [Presentation] 新規小胞体品質管理システムの分子機構の解明 (2012)
  • Author(s): 門脇寿枝,一條秀憲,西頭英起
  • Organizer: 第7回臨床ストレス応答学会大会
  • Place of Presentation: 東京
• [Presentation] 新規小胞体品質管理システムの分子機構の解明 (2012)
  • Author(s): 門脇寿枝,一條秀憲,西頭英起
  • Organizer: 第85回日本生化年会
  • Place of Presentation: 福岡市
• [Presentation] 小胞体の品質管理システムとその破綻による疾患
  • Author(s): 西頭英起
  • Organizer: 埼玉医科大学卒後教育委員会講演学術集会
  • Place of Presentation: 埼玉医科大学
  • Invited