Possible Interaction: Ethanol and Sirolimus

“ Alcohol‐related decrease in mechanistic target of rapamycin (mTOR) and Ras homolog enriched in brain (Rheb), that initiate autophagy, correlated with increased Beclin1 and autophagy‐related protein 7 (Atg7), proteins involved in phagophore‐autophagosome formation, in ALD.”

“ Rapamycin with ethanol up‐regulated autophagy and SF1 expression and activated steroidogenesis when compared with ethanol alone.”

“Pharmacological intervention with rapamycin alleviated the ability of alcohol to up‐regulate lipogenesis, to down‐regulate fatty acid oxidation, and to induce steatogenic phenotypes.”

“Interestingly, incubation of cultured cells with rapamycin prevented ethanol effects on autophagic flux, ethanol-induced cell death and vascular plasticity.”

“The increase of autophagic vacuole number may be due to excessive autophagosome formation associated with the partial inhibition of the mammalian target of rapamycin pathway upon ethanol exposure.”

“Stimulation of autophagy by rapamycin blunted the elevated steatosis produced by binge ethanol.”

“Furthermore, we postulated that both perillyl alcohol and rapamycin disrupted this complex to control telomerase activity post-translationally.”

“As cells were exposed to alcohol , the levels of LC3-II proteins became elevated, likewise, pre-treatment with 3-methyladenine (3-MA, an autophagic inhibitor) or rapamycin (an autophagic inducer) resulted in an increased or decreased percentage of apoptosis in contrast to other alcohol-treated groups, respectively.”

“Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury.”

“ Alcohol (EtOH) decreases protein synthesis and mammalian target of rapamycin (mTOR)-mediated signaling and blunts the anabolic response to growth factors in skeletal muscle.”

“ Chronic ethanol consumption decreased protein expression of LC3 lipidation-related proteins Atg3 and Atg7, and the lysosomal proteins lysosome-associated membrane protein-2 and Rab7, and increased the protein expression of calpain 1 and phosphorylated mammalian target of rapamycin.”