ReferenceID 196
Ginseng metabolite Protopanaxadiol induces Sestrin2 expression and AMPK activation through GCN2 and PERK
Cell Death Dis
Ginseng is one of the most commonly used herbs that is believed to have a variety of biological activities, including reducing blood sugar and cholesterol levels, anti-cancer, and anti-diabetes activities. However, litt
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Record Fields
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- Reference Id
- 196
- Evidence Id
- 16786
- Core Evidence Id
- 16786
- Source Reference Id
- 355
- Herb2 Reference Id
- HBREF000646
- Subject Paper Key
- HBIN040932_30952841
- Pubmed Id
- 30952841
- Doi
- 10.1038/s41419-019-1548-7
- Paper Title
- Ginseng metabolite Protopanaxadiol induces Sestrin2 expression and AMPK activation through GCN2 and PERK
- Paper Abstract
- Ginseng is one of the most commonly used herbs that is believed to have a variety of biological activities, including reducing blood sugar and cholesterol levels, anti-cancer, and anti-diabetes activities. However, little is known about the molecular mechanisms involved. In this study, we showed that protopanaxadiol (PPD), a metabolite of the protopanaxadiol group ginsenosides that are the major pharmacological constituents of ginsengs, significantly altered the expression of genes involved in metabolism, elevated Sestrin2 (Sesn2) expression, activated AMPK, and induced autophagy. Using CRISPR/CAS9-mediated gene editing and shRNA-mediated gene silencing, we demonstrated that Sesn2 is required for PPD-induced AMPK activation and autophagy. Interestingly, we showed that PPD-induced Sesn2 expression is mediated redundantly by the GCN2/ATF4 amino acid-sensing pathway and the PERK/ATF4 endoplasmic reticulum (ER) stress pathway. Our results suggest that ginseng metabolite PPD modulates the metabolism of amino acids and lipids, leading to the activation of the stress-sensing kinases GCN2 and PERK to induce Sesn2 expression, which promotes AMPK activation, autophagy, and metabolic health.
- Journal
- Cell Death Dis
- Publish Year
- 2019
- Experiment Subject
- human colorectal cancer cells hct116
- Experiment Type
- Cell Experiment
- Phenotype Related
- Cancer; Diabetes
- Paper Title Cn
- Paper Title En
- Ginseng metabolite Protopanaxadiol induces Sestrin2 expression and AMPK activation through GCN2 and PERK
- Bilingual Status
- semi_complete