| RRC ID |
36732
|
| 著者 |
Jegal KH, Ko HL, Park SM, Byun SH, Kang KW, Cho IJ, Kim SC.
|
| タイトル |
Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress.
|
| ジャーナル |
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.
|
| 巻・号 |
21(5)
|
| ページ |
642-56
|
| 公開日 |
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
|
| 引用数 |
18
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pGL4-phSESN2 (RDB07413) |
