2,5-Hexanedione induces autophagic death of VSC4.1 cells via a PI3K/Akt/mTOR pathway

Abstract

2,5-Hexanedione (HD) is an important bioactive metabolite of n-hexane, which mediates the neurotoxicity of the parent compound. Increasing evidence suggests that over-activated autophagy can lead to autophagic neuronal death; however, whether the excessive autophagy is involved in HD-induced neurotoxicity remains unknown. To investigate the effect of HD on autophagy and to find its underlying mechanism, we respectively treated VSC4.1 cells with 5, 15 and 25 mM HD for 24 h. Our results show that HD induced excessive autophagy of VSC4.1 cells in a dose-dependent manner, also, the over-activated autophagy was significantly mitigated in the presence of PI3K activator or Akt activator or mTOR activator. These results indicate that HD induces excessive autophagy of VSC4.1 cells by repressing the PI3K/Akt/mTOR signaling pathway. LDH assay showed that HD contributed to a concentration dependent increase in VSC4.1 cell death, which was significantly reduced by the administration of PIK-III, an autophagy inhibitor. These results also indicate that HD induces autophagic death of VSC4.1 cells via the signaling pathway.

MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway

“…Previous study reported that PI3K/Akt/mTOR pathway played an important role in regulating autophagy [ 22 ]. Therefore, we further explored whether miR-361-5p suppressed chemoresistance of GC cells through PI3K/Akt/mTOR pathway.…”

Exendin‐4 and Liraglutide Attenuate Glucose Toxicity‐Induced Cardiac Injury through mTOR/ULK1‐Dependent Autophagy

“…To assess whether high glucose affects autophagy, H9c2 cells were exposed with high glucose medium in the absence or presence of Exe (10 nM) or LIRA (100 nM) in the presence or absence of the autophagy inducer rapamycin (100 nM) or the autophagy inhibitor 3-methyladenine (3-MA, 10 mM) [ 23 ]. To assess the role of mTOR in Exe- and LIRA-induced response, if any, against high glucose-induced cardiomyocyte mechanical dysfunction, murine cardiomyocytes were exposed with high glucose medium in the absence or presence of Exe (10 nM) or LIRA (100 nM) for 4 hours with or without the mTOR activator [3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO),120 μ M] [ 24 ] prior to assessment of mechanical function.…”

Retracted Article: Vitexin mitigates myocardial ischemia reperfusion-induced damage by inhibiting excessive autophagy to suppress apoptosis via the PI3K/Akt/mTOR signaling cascade

“…Autophagy is mediated by various signal pathways, most of which were related to the PI3K/Akt/mTOR signaling pathway. 18 Here, we measured the expression of phosphorylated Akt (p-Akt) and mTOR in different groups by western blot. Our data showed that the low expression of p-Akt and mTOR induced by MI/R injury was up-regulated by vitexin treatment in a dosedependent manner (**P < 0.01, # P < 0.05, ## P < 0.01, Fig.…”