RRC ID 36732
Author Jegal KH, Ko HL, Park SM, Byun SH, Kang KW, Cho IJ, Kim SC.
Title Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress.
Journal Apoptosis
Abstract Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) has many pharmacological activities including anti-inflammation, anti-oxidant and anti-cancer effects. Autophagy is the basic cellular machinery involving the digestion of damaged cellular components. In the present study, we investigated the protection effects of eupatilin against arachidonic acid (AA) and iron-induced oxidative stress in HepG2 cells and tried to elucidate the molecular mechanisms responsible. Eupatilin increased cell viability against AA + iron in a concentration-dependent manner and prevented mitochondrial dysfunction and reactive oxygen species (ROS) production. In addition, AA + iron increased the levels of pro-apoptotic proteins and these changes were prevented by eupatilin. Eupatilin also induced autophagy, as evidenced by the accumulation of microtubule-associated protein 1 light chain3-II and the detection of autophagic vacuoles. Furthermore, the protective effects of eupatilin on mitochondrial dysfunction and ROS production were significantly abolished by autophagy inhibitors. Eupatilin also increased the mRNA level of sestrin-2 and its promoter-driven reporter gene activity, which resulted in the up-regulation of sestrin-2 protein. Finally, gene silencing using sestrin-2 siRNA and the ectopic expression of recombinant adenoviral sestrin-2 indicated that sestrin-2 induction by eupatilin was required for autophagy-mediated cytoprotection against AA + iron. Our results suggest that eupatilin activates sestrin-2-dependent autophagy, thereby preventing oxidative stress induced by AA + iron.
Volume 21(5)
Pages 642-56
Published 2016-5-1
DOI 10.1007/s10495-016-1233-6
PII 10.1007/s10495-016-1233-6
PMID 27015669
MeSH Animals Apoptosis / drug effects Arachidonic Acid / toxicity Autophagy* Cell Line Flavonoids / pharmacology* Hep G2 Cells Hepatocytes / drug effects* Hepatocytes / metabolism Hepatocytes / physiology Humans Iron / toxicity Mitochondria, Liver / drug effects Mitochondria, Liver / metabolism Mitochondria, Liver / physiology Nuclear Proteins / biosynthesis Nuclear Proteins / metabolism* Oxidative Stress* Rats Reactive Oxygen Species / metabolism
IF 4.543
Times Cited 18
DNA material pGL4-phSESN2 (RDB07413)