Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8286558 | Redox Biology | 2018 | 53 Pages |
Abstract
Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. In addition, trehalose functions as an antioxidant though its underlying molecular mechanisms remain unclear. In this study, we showed that trehalose not only promoted autophagy, but also increased p62 protein expression, in an autophagy-independent manner. In addition, trehalose increased nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in a p62-dependent manner and enhance expression of its downstream antioxidant factors, heme oxygenase-1 (Ho-1) and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (Nqo1). Moreover, treatment with trehalose significantly reduced amount of reactive oxygen species. Collectively, these results suggested that trehalose can function as a novel activator of the p62-Keap1/Nrf2 pathway, in addition to inducing autophagy. Therefore, trehalose may be useful to treat many chronic diseases involving oxidative stress and dysfunction of autophagy.
Keywords
ATGNAFLDRFPNQO1Heme oxygenase-1MCP1p62LC3HFDRT-PCRmTORshRNADMEMMEFGFPHO-1Nrf2keap1Dulbecco's modified Eagle Mediumsmall hairpin RNAAntioxidantAutophagyNon-alcoholic steatohepatitisnon-alcoholic fatty liver diseaseTrehaloseOxidative stressHigh fat dietnuclear factor (erythroid-derived 2)-like 2mouse embryonic fibroblastNash Mechanistic target of rapamycinreverse transcription polymerase chain reactionmonocyte chemoattractant protein-1green fluorescent proteinKelch-like ECH-associated protein 1autophagy-related gene
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Yuhei Mizunoe, Masaki Kobayashi, Yuka Sudo, Shukoh Watanabe, Hiromine Yasukawa, Daiki Natori, Ayana Hoshino, Arisa Negishi, Naoyuki Okita, Masaaki Komatsu, Yoshikazu Higami,