Trehalose protects against oxidative stress by regulating the Keap1–Nrf2 and autophagy pathways

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.

Advances in present‐day frozen dough technology and its improver and novel biotech ingredients development trends—A review

“…Trehalose prevents protein denaturation by slowing rate of polyglutamine mediated protein aggregation and resultant pathogenesis by stabilizing an aggregation prone model protein; during freeze stress, helping retain yeast cellular integrity (Mizunoe et al, 2017;Stefanello et al, 2018;Zhang, Oldenhof, Sieme, & Wolkers, 2016). Trehalose prevents protein denaturation by slowing rate of polyglutamine mediated protein aggregation and resultant pathogenesis by stabilizing an aggregation prone model protein; during freeze stress, helping retain yeast cellular integrity (Mizunoe et al, 2017;Stefanello et al, 2018;Zhang, Oldenhof, Sieme, & Wolkers, 2016).…”

“…The accumulated intracellular molecules impact yeast functionality differently. Trehalose prevents protein denaturation by slowing rate of polyglutamine mediated protein aggregation and resultant pathogenesis by stabilizing an aggregation prone model protein; during freeze stress, helping retain yeast cellular integrity (Mizunoe et al, 2017;Stefanello et al, 2018;Zhang, Oldenhof, Sieme, & Wolkers, 2016). Proline, on the other hand, combines with intracellular free water to form strong hydrogen bonds and, at high levels, is associated with high level of superoxide dismutase which lowers levels of reactive oxygen species, preventing intracellular substances from oxidation (Sasano et al, 2012).…”

Microtubule Defect Involved in ‘Mitophagy Resistance’ Under Subacute Oxidative Stress - Potential Mechanism for Cellular Inflammation

“…Autophagy is a cellular housekeeping system that mediates either bulk removal of cellular components or selective degradation of damaged organelles and protein aggregates [8]. Its defect or derangement in signals is associated with pathogenesis of various diseases such as cancer, neurodegeneration, metabolic diseases and multiple organ failure of critically illness [9]. Autophagy plays an essential role in the skeletal muscle system, maintaining muscle fiber integrity [10].…”

“…Some studies have suggested that trehalose helps maintain MT-forming function of tubulins [29]. By employing the cell-protective and autophagy-augmenting proficiency of trehalose, therapeutic studies have been proposed to treat several diseases in which autophagy plays an important role [9]. This study therefore examined whether normalizing the disturbed MTs with trehalose can prevent the mitophagy dysfunction under the subacute oxidative stress.…”

Effect of trehalose on manganese‐induced mitochondrial dysfunction and neuronal cell damage in mice

“…Tre exerts beneficial effects under several conditions, such as oxidative damage, dehydration and temperature changes . Increasing evidence demonstrates that Tre plays a vital role on anti‐apoptosis effects through ameliorating mitochondria dysregulation, resistance to oxidation and restoring autophagic flux . Although Tre could alleviate neuronal cell injury in vivo, whether Tre could attenuate Mn‐induced mitochondrial dysfunction in basal ganglia is unknown.…”