Immunohistochemical study of relationship between autophagy marker LC3 and nutritional state in human livers.

• Project/Area Number: 24590851
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: NAKAJIMA Makoto 東京大学, 医学(系)研究科(研究院), 技術専門員 (70396696)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Kenichi 東京大学, 大学院医学系研究科, 教授 (40166947)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: オートファジー / 肝臓 / LC3 / 免疫染色 / Autophagy / 飢餓 / 脂肪肝 / ＬＣ3

Outline of Final Research Achievements

Microｔubule-associated protein 1 light chain 3 (LC3) immunohistochemistry reproducibly delineated puncta in normal human liver, which were preferentially located around the central venal zone. The extent of LC3 immunostaining reduced as progressing steatosis. Double immunofluorescence for Adipose differentiation -related protein (ADRP) and LC3 demonstreted that positive area of the twe protein have inverse relationship, as well as that they are co-localization on the membrane of small lipid droplets ( LDs) but not of large LDs.
These findings suggest that impaired autophagy promotes steatosis and that autophagy may be implicated in LD turnover.

Research Products

• [Journal Article] Immunohistochemical study of the autophagy marker microtubule-associated protein 1 light chain 3 in normal and steatotic humanlivers (2013)
  • Author(s): Kashima J, Shintani-Ishida K, Nakajima M, Maeda H, Unuma K, Uchiyama Y, Yoshida K
  • Journal Title: Hepatol Res Volume: 413 Issue: 7 Pages: 779-787
  • DOI: 10.1111/hepr.12183
  • Peer Reviewed / Open Access
• [Journal Article] Inducer of hemeoxygenase-1 cobalt protoporphyrin accelerates autophagy and suppresses oxidative damages during lipopolysaccharide treatment in rat liver. (2013)
  • Author(s): Unuma K, Aki T, Matsuda S, Yoshida K et al.
  • Journal Title: Hepatol Res. Volume: 43(1) Pages: 91-96
  • NAID: 10031183462
  • Peer Reviewed
• [Journal Article] MDMA induces cardiac contractile dysfunction through autophagy upregulation and lysosome destabilization in rats. (2013)
  • Author(s): Shintani-Ishida K, Saka K, Yamaguchi K, Hayashida M, Nagai H, Takemura G, Yoshida K.
  • Journal Title: Biochim Biophys Acta (molecular basis of disease) Volume: 1842(5) Pages: 691-700
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of autophagy maker LC3 in human livers related to steatosis (2012)
  • Author(s): 加島淳平、前田秀将、中嶋 信、吉田謙一
  • Journal Title: 日本法医学雑誌 Volume: 66 Pages: 106-106
• [Presentation] Fatty liver disease induced by intermittent hypoxia in rat fed on high-fat diet. (2013)
  • Author(s): 加島淳平、前田秀将、山口るつ子、永井恒志、坂幹樹、吉田謙一
  • Organizer: 第97次日本法医学会学術全国集会
  • Place of Presentation: 札幌 ロイトン札幌
• [Presentation] Immunohistochemical detection of autophagy maker LC3 in human livers related to steatosis (2012)
  • Author(s): 加島淳平、前田秀将、中嶋 信、吉田謙一
  • Organizer: 第96次日本法医学会学術全国集会
  • Place of Presentation: 静岡県 浜松市 アクトシティ浜松