RRC ID 52393
Author Mizunoe Y, Kobayashi M, Sudo Y, Watanabe S, Yasukawa H, Natori D, Hoshino A, Negishi A, Okita N, Komatsu M, Higami Y.
Title Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways.
Journal Redox Biol
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.
Volume 15
Pages 115-124
Published 2018-5-1
DOI 10.1016/j.redox.2017.09.007
PII S2213-2317(17)30544-X
PMID 29241092
PMC PMC5730428
MeSH Animals Autophagy / genetics Autophagy-Related Protein 5 / genetics Heme Oxygenase-1 / genetics Humans Kelch-Like ECH-Associated Protein 1 / genetics* Membrane Proteins / genetics Mice Mice, Knockout NAD(P)H Dehydrogenase (Quinone) / genetics NF-E2-Related Factor 2 / genetics* Oxidative Stress / drug effects Proto-Oncogene Proteins c-yes / genetics* Signal Transduction / drug effects TOR Serine-Threonine Kinases / genetics Trehalose / metabolism Trehalose / pharmacology*
IF 9.986
Times Cited 47
Human and Animal Cells Hepa 1-6(RCB1638)