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MHY1485, in a culture system by using Ac2F rat hepatocytes. Autophagic flux was measured to evaluate the autophagic activity. Autophagosomes were visualized in Ac2F cells transfected with AdGFP-LC3 by live-cell confocal microscopy. In addition, activity of mTOR, a major regulatory protein of autophagy, was assessed by western blot and docking simulation using AutoDock 4.2. In the result, treatment with MHY1485 suppressed the basal autophagic flux, and this inhibitory effect was clearly confirmed in cells under starvation, a strong physiological inducer of autophagy. The levels of p62 and beclin-1 did not show significant change after treatment with MHY1485. Decreased co-localization of autophagosomes and lysosomes in confocal microscopic images revealed the inhibitory effect of MHY1485 on lysosomal fusion during starvation-induced autophagy. These effects of MHY1485 led to the accumulation of LC3II and enlargement of the autophagosomes in a dose- and time- dependent manner. Furthermore, MHY1485 induced mTOR activation and correspondingly showed a higher docking score than PP242, a well-known ATP-competitive mTOR inhibitor, in docking simulation. In conclusion, MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. The significance of this study is the finding of a novel inhibitor of autophagy with an mTOR activating effect. For the detailed information of GSK-503, the solubility of GSK-503 in water, the solubility of GSK-503 in DMSO, the solubility of GSK-503 in PBS buffer, the animal experiment (test) of GSK-503, the cell expriment (test) of GSK-503, the in vivo, in vitro and clinical trial test of GSK-503, the EC50, IC50,and affinity,of GSK-503, For the detailed information of GSK-503, the solubility of GSK-503 in water, the solubility of GSK-503 in DMSO, the solubility of GSK-503 in PBS buffer, the animal experiment (test) of GSK-503, the cell expriment (test) of GSK-503, the in vivo, in vitro and clinical trial test of GSK-503, the EC50, IC50,and affinity,of GSK-503, Please contact DC Chemicals. |
