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Study of a novel NF-kappaB-regulating protein, Nucling, in the development of non-alcoholic fatty liver diseases

Research Project

Project/Area Number 25460388
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionTokushima Bunri University (2014-2015)
The University of Tokushima (2013)

Principal Investigator

SAKAI TAKASHI  徳島文理大学, その他の研究科, 教授 (80284321)

Co-Investigator(Kenkyū-buntansha) FUKUI Kiyoshi  徳島大学, 疾患酵素学研究センター, 教授 (00175564)
Research Collaborator Dang Huy Van  
Pham Tuan Anh  
Tran Diem Hong  
Kim Sun Mi  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsNAFLD / Nucling / NF-κB / metabolic syndrome / insulin resistance / 炎症性疾患 / アポトーシス / NFκB / ヌクリング / 離乳後乳腺退縮現象 / STAT3 / メタボリック症候群
Outline of Final Research Achievements

Nonalcoholic fatty liver disease, NAFLD, is a cause of a fatty liver not due to excess alcohol use, which is related to insulin resistance and metabolic abnormalities. Here, we found that Nucling-KO mice develop hallmark features of NAFLD. We hypothesized that these metabolic changes might correlate with the accumulation of oxidative stress in liver, and malfunction of insulin regulation in pancreas. Nucling deficiency promoted the accumulation of reactive oxygen species in liver of mice. High fat diet revealed dysregulation of insulin expression in the Nucling-KO mice. We also found that glucose-induced insulin up-regulation requires NF-κB activation, which is dysregulated in Nucling-KO mice. These results suggest that defect of the Nucling-NF-κB system promoted the malfunction of insulin transcription resulted in development of metabolic disorders including NAFLD. In conclusion, we propose that NF-κB signal is important for the homeostatic regulation of insulin transcription.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (27 results)

All 2015 2014 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] 1)Nucling, a novel apoptosis-associated protein, controls mammary gland involution by regulating NF-κB and STAT32015

    • Author(s)
      Dang HV, Sakai T, Pham TA, Tran DH, Yorita K, Shishido Y, Fukui K.
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 40 Pages: 24626-24635

    • DOI

      10.1074/jbc.m115.673848

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification of DNA-binding proteins that interact with the 5'-flanking region of the human D-amino acid oxidase gene by pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry.2015

    • Author(s)
      Tran DH, Shishido Y, Chung SP, Trinh HTT, Yorita K, Sakai T, Fukui K.
    • Journal Title

      J Pharm Biomed Anal.

      Volume: in press Pages: 94-100

    • DOI

      10.1016/j.jpba.2015.02.031

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of two promoters for human d-amino acid oxidase gene: implication for the differential promoter regulation mediated by PAX5/PAX2.2015

    • Author(s)
      Tran DH, Shishido Y, Chung SP, Trinh HT, Yorita K, Sakai T, Fukui K.
    • Journal Title

      J Biochem.

      Volume: 157(5) Issue: 5 Pages: 377-387

    • DOI

      10.1093/jb/mvu084

    • NAID

      40020461475

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] D-アミノ酸代謝の病態システム酵素学:統合失調症疾患感受性とD-アミノ酸酸化酵素2014

    • Author(s)
      福井清、宍戸裕二、頼田和子、坂井隆志
    • Journal Title

      月刊バイオインダストリー

      Volume: 31 Pages: 11-16

    • Related Report
      2013 Research-status Report
  • [Presentation] Nucling, a novel apoptosis-associated protein, controls Mammary Gland involution by regulation NF-κB and STAT32015

    • Author(s)
      5)Van Huy Dang, T. Sakai, Anh Tuan Pham, Hong Diem Tran, K. Yorita, Y. Shishido, K. Fukui.
    • Organizer
      1st International Symposium on Molecular Medicine in Tokushima University
    • Place of Presentation
      徳島県徳島市
    • Year and Date
      2015-12-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Poly(I:C) stimulation-induced microglial activation is regulated by Nucling signal2015

    • Author(s)
      2)Anh Tuan Pham, T. Sakai, Van Huy Dang, Y. Shishido, K. Yorita, K. Fukui
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド, 兵庫
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] Chiral Science and Pathophysiology of Amino Acid Metabolism: regulation of human D-amino acid oxidase gene expression and implication for human2015

    • Author(s)
      4)Diem Hong Tran, Y. Shishido, Seong Pil Chung, Huong Thi Thanh Trinh, K. Yorita, T. Sakai, K. Fukui
    • Organizer
      14th FAOBMB Congress and 84th Annual Meeting of SBC (I)
    • Place of Presentation
      BITS Pilani Hyderabad、インド
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Search for the regulation of human D-amino acid oxidase gene, a potential risk factor of schizophrenia2015

    • Author(s)
      2)Diem Hong Tran, Y. Shishido, Seong Pil Chung, Huong Thi Thanh Trinh, K. Yorita, T. Sakai, K. Fukui
    • Organizer
      The Second Gene and Immunotherapy Conference in Vietnam
    • Place of Presentation
      ベトナム・ホーチミン市
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nucling, a novel apoptosis-associated protein, controls postlactational involution of mammary gland through regulation of NF-κB and STAT32015

    • Author(s)
      3)Van Huy Dang, T. Sakai, Anh Tuan Pham, Hong Diem Tran, K. Yorita, Y. Shishido, K. Fukui
    • Organizer
      The Second Gene and Immunotherapy Conference in Vietnam
    • Place of Presentation
      ベトナム・ホーチミン市
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nucling, an apoptosis-associated novel protein, controls mammary gland involution through regulation of NF-B and STAT32015

    • Author(s)
      1)Van Huy Dang, T. Sakai, Anh Tuan Pham, Hong Diem Tran, K. Yorita, Y. Shishido, K. Fukui
    • Organizer
      The 10th International Symposium of the Institute Network
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2015-07-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトD-アミノ酸酸化酵素遺伝子の発現調節機構:2つのプロモーター領域の同定とその調節2015

    • Author(s)
      1)Diem Hong Tran, Y. Shishido, Seong Pil Chung, Huong Thi Thanh Trinh, K. Yorita, T. Sakai, K. Fukui
    • Organizer
      日本ビタミン学会第67回大会
    • Place of Presentation
      奈良春日野国際フォーラム 甍
    • Year and Date
      2015-06-06
    • Related Report
      2015 Annual Research Report
  • [Presentation] 5)Nucling, an apoptosis-associated novel protein, controls mammary gland involution through regulation of NF-κB and STAT3.2015

    • Author(s)
      Huy Van Dang
    • Organizer
      The meeting of Stress & Nutrition Cluster
    • Place of Presentation
      徳島大学
    • Year and Date
      2015-01-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 3)Nucling, an apoptosis-associated novel protein, controls the postlactational involution of mammary gland through regulation of NF-κB and STAT3.2014

    • Author(s)
      Huy Van Dang
    • Organizer
      第87回日本生化学会年会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 4)Nucling, an apoptosis-associated novel protein, controls the postlactational involution of mammary gland through regulation of NF-κB and STAT3.2014

    • Author(s)
      Huy Van Dang
    • Organizer
      Tokushima Bioscience Retreat
    • Place of Presentation
      小豆島
    • Year and Date
      2014-09-18 – 2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 1)D-AMINO ACID METABOLISM IN HEALTH AND DISEASES: PATHOPHYSIOLOGICAL BASES FOR SCHIZOPHRENIA AND CANCER GENE THERAPY.2014

    • Author(s)
      Fukui K
    • Organizer
      The 2nd International Conference of D-Amino Acid Research
    • Place of Presentation
      宇都宮市
    • Year and Date
      2014-09-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 2)Identification of promoter region of human D-amino acid oxidase (hDAO) gene and its interacting proteins - Search for the regulation of hDAO expression.2014

    • Author(s)
      Tran DH
    • Organizer
      The 9th International Symposium of the Institute Network
    • Place of Presentation
      大阪府吹田市
    • Year and Date
      2014-06-19
    • Related Report
      2014 Research-status Report
  • [Presentation] 2)Induction and regulation of gene expression of D-amino acid oxidase in glial and kidney cells.2014

    • Author(s)
      Tran DH
    • Organizer
      日本ビタミン学会第66回大会
    • Place of Presentation
      兵庫県姫路市
    • Year and Date
      2014-06-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 1)Loss of Nucling promotes delayed mammary gland involution through suppression of NF-κB and STAT3.2014

    • Author(s)
      Huy Van Dang
    • Organizer
      日本生化学会中国四国支部例会
    • Place of Presentation
      愛媛大学
    • Year and Date
      2014-06-06 – 2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規アポトーシス誘導因子ヌクリングのホモシステイン代謝系及び神経性心疾患への関与の検討

    • Author(s)
      坂井隆志、佐古有季哉、本城勇樹、中嶋広太、Dang Van Huy, Pham Anh Tuan, 宍戸裕二、頼田和子、福井清
    • Organizer
      日本ビタミン学会第66回大会
    • Place of Presentation
      姫路商工会議所(兵庫県)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヌクリング遺伝子欠損マウスは非アルコール性脂肪性肝障害 (NAFLD)とインスリン発現異常をもたらす

    • Author(s)
      坂井 隆志, 佐古 有季哉, Huy Van Dang, Anh Tuan Pham, 福井 清
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Research-status Report
  • [Presentation] Medical Aspects of D-Amino Acid Metabolism: Molecular Target for Cancer Gene Therapy and Schizophrenia

    • Author(s)
      Kiyoshi Fukui, Yoshiteru Urai, Hwan Ki Park, Tomoya Kawazoe, Sanae Iwana, Koji Ono, Rabab M. Abou El-Magd, Seong Pil Chung, Salah M. El Sayed, Diem Hong Tran, Yuji Shishido, Kazuko Yorita, Takashi Sakai
    • Organizer
      FAOBMB Mini-Symposium-Molecular Bases for Medical and Pharmaceutical Sciences-
    • Place of Presentation
      岩手医科大学(岩手県)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Identification of promoter region of human D-amino acid oxidase (hDAO) gene and its interacting proteins - Search for the regulation of hDAO expression

    • Author(s)
      Diem Hong Tran, Yuji Shishido, Huong Thi Thanh Trinh, Kazuko Yorita, Takashi Sakai, Kiyoshi Fukui
    • Organizer
      The 9th International Symposium of the Institute Network
    • Place of Presentation
      大阪大学(大阪府)
    • Related Report
      2013 Research-status Report
  • [Presentation] Induction and regulation of gene expression of in LLC-PK1 cells

    • Author(s)
      Diem Hong Tran, Yuji Shishido, Kazuko Yorita, Takashi Sakai, Kiyoshi Fukui
    • Organizer
      第54回日本生化学会中国・四国支部例会
    • Place of Presentation
      徳島大学(徳島県)
    • Related Report
      2013 Research-status Report
  • [Presentation] 哺乳動物におけるD-アミノ酸酸化酵素遺伝子の発現誘導機構の解析

    • Author(s)
      宍戸裕二、森本佳奈、Diem Hong Tran、Tuan Anh Pham、曽我部弘史、頼田和子、坂井隆志、福井清
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Research-status Report
  • [Presentation] Induction and regulation of gene expression of D-amino acid oxidase in LLC-PK1 cells

    • Author(s)
      Diem Hong Tran, Yuji Shishido, Huong Thi Thanh Trinh, Kazuko Yorita, Takashi Sakai, Kiyoshi Fukui
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Research-status Report
  • [Presentation] Delayed mammary gland involution in Nucling-KO mice

    • Author(s)
      Huy Van Dang, Takashi Sakai, Tuan Anh Pahm, Diem Hong Tran, Kazuko Yorita, Takashi Sakai, Kiyoshi Fukui
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Research-status Report
  • [Presentation] Induction and regulation of gene expression of D-amino acid oxidase in LLC-PK1 cells

    • Author(s)
      Diem Hong Tran, Yuji Shishido, Huong Thi Thanh Trinh, Kazuko Yorita, Takashi Sakai, Kiyoshi Fukui
    • Organizer
      第9回 D-アミノ酸研究会学術講演会
    • Place of Presentation
      関西大学(大阪府)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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