title: Trehalose activates autophagy and decreases proteasome inhibitor-induced endoplasmic reticulum stress and oxidative stress-mediated cytotoxicity in hepatocytes.
abstract: OBJECTIVE
  Endoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative stress, cytoplasmic inclusion body formation, and apoptosis in hepatocytes. Autophagy is a bulk degradation pathway for long-lived cytoplasmic proteins or damaged organelles and is also a major degradation pathway for many aggregate-prone and disease-causing proteins. We previously reported that rapamycin, a mammalian target of rapamycin inhibitor, activated autophagy and decreased proteasome inhibitor-mediated ubiquitinated protein accumulation, cytoplasmic inclusion body formation, and apoptosis in hepatocytes. Trehalose is a non-reducing disaccharide that has been shown to activate autophagy. It has been reported to decrease aggregate-prone proteins and ameliorate cytotoxicity in neurodegenerative disease models. However, the effects of trehalose in hepatocytes are unclear.
  
  
  METHODS
  We show here that trehalose activated autophagy and reduced endoplasmic reticulum stress, cytoplasmic inclusion body formation, and apoptosis in proteasome inhibitor-treated liver-derived cultured cells.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report showing that trehalose activates autophagy and has cytoprotective effects in hepatocytes. Our findings suggest that trehalose can become a therapeutic agent for endoplasmic reticulum stress-related liver diseases.
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Honma
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sato-Morita
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Katsuki
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mihara
authors.affiliation: Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Baba
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Harada
keywords: autophagy; cytoplasmic inclusion body; disaccharide; endoplasmic reticulum stress; mammalian target of rapamycin; proteasome