Cetrimonium bromide promotes the clearance of lipids by activating the TFEB-mediated autophagosome-lysosome pathway in hepatic cells
| Autor: | Zhichen Shi, Dianlong Li, Junting Xu, Li Tao, Qing Zhao, Jieru Lin, Aipo Diao, Zhenxing Liu, Xinpeng Zhang, Xu Wang, Yuyin Li |
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| Rok vydání: | 2021 |
| Předmět: |
Autophagosome
Chemistry Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cetrimonium Autophagy Autophagosomes Lipid metabolism Cell Biology Metabolism Lipid Metabolism Biochemistry Cell biology medicine.anatomical_structure Lysosome Hepatic stellate cell medicine Hepatocytes TFEB Humans RNA Small Interfering Lysosomes Molecular Biology Biogenesis Cells Cultured |
| Zdroj: | Biochemistry and cell biology = Biochimie et biologie cellulaire. 99(5) |
| ISSN: | 1208-6002 |
| Popis: | Autophagy plays a key role in the metabolism of macromolecules via the degradative abilities of the lysosome. Transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Herein, we report that cetrimonium bromide (CTAB; a quaternary ammonium compound) promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. Knockdown of TFEB mediated by short hairpin RNA inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt–mTORC1 signaling pathway. Moreover, CTAB treatment significantly increases lipid metabolism in both palmitate- and oleate-treated HepG2 cells, and this increase was attenuated by knockdown of TFEB. Collectively, our results indicate that CTAB activates the autophagosome–lysosome pathway via inducing the nuclear translocation of TFEB by inhibiting the mTORC1 signaling pathway. These results add to the collective understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism. |
| Databáze: | OpenAIRE |
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