Ferulic Acid Induces Mammalian Target of Rapamycin Inactivation in Cultured Mammalian Cells
| Autor: | Junji Ezaki, Takashi Ueno, Dong-Mei Zheng, Norihiro Tada, Juan Alejandro Oliva Trejo, Zehua Bian, Norihiko Furuya |
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| Rok vydání: | 2013 |
| Předmět: |
Antioxidant
Coumaric Acids medicine.medical_treatment Cell Pharmaceutical Science Biology Ferulic acid Dephosphorylation Mice chemistry.chemical_compound Autophagy medicine Animals Humans Cells Cultured PI3K/AKT/mTOR pathway Pharmacology Kinase Activator (genetics) Ribosomal Protein S6 Kinases TOR Serine-Threonine Kinases General Medicine Mice Inbred C57BL medicine.anatomical_structure chemistry Biochemistry Hepatocytes HeLa Cells |
| Zdroj: | Biological and Pharmaceutical Bulletin. 36:120-124 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b12-00695 |
| Popis: | Ferulic acid (FA), a naturally occurring polyphenol abundant in vegetables and rice bran, is known to possess a potent antioxidant activity, thereby protecting cells from oxidative stress. In the present study, we show that in addition to its known anti-oxidant activity, ferulic acid exerts substantial inhibitory activity on cellular mammalian target of rapamycin (mTor)-signaling pathways. In HeLa cells and mouse primary hepatocytes cultured with conventional nutrient-rich media, ferulic acid (1 mM) elicited dephosphorylation of S6 kinase and its substrate ribosomal S6. The dephosphorylating activity of ferulic acid was almost comparable to that of rapamycin, an established mTor inhibitor (TORC1). We next investigated the effect of ferulic acid on autophagy, a major cellular degradative process, which significantly contributes to the maintenance of cell homeostasis. Using a conventional green fluorescent protein-microtubule-associated protein IA/IB light chain 3 (GFP-LC3) dot assay to evaluate autophagy flux, we showed that ferulic acid caused a significant increase in GFP-LC3 dots under serum-rich conditions in HeLa cells. The enhancement of autophagic flux by ferulic acid was almost equivalent to that of rapamycin. Furthermore, ferulic acid significantly enhanced autophagic degradation of (14)C-leucine-labeled long-lived proteins of cultured mouse hepatocytes under nutrient-rich conditions, but not nutrient-deprived conditions. These results indicate that ferulic acid is almost the equivalent of rapamycin in the ability to inhibit mTor (TORC1), which makes it a potent activator of basal autophagy. |
| Databáze: | OpenAIRE |
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