3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes.
3-Methyladenine (5 mM) inhibits endogenous protein degradation in isolated rat hepatocytes by about 60%, while having no adverse effect on the degradation of an exogenous protein (asialofetuin), on protein synthesis, or on intracellular ATP levels. 3-Methyladenine appears to act specifically upon the autophagic/lysosomal pathway of degradation, as judged from its lack of effect in the presence of amino acids or a lysosomotropic amine (propylamine). The effect of the purine is not mediated by amino acids because the inhibition of protein degradation is accompanied by a significant depression of intracellular amino acid levels. The ability of 3-methyladenine to suppress the formation of electron microscopically visible autophagosomes suggests that it may be regarded as a specific inhibitor of autophagy.
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001329:Autolysis / Q000503:physiopathology; D002478:Cells, Cultured; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D000596:Amino Acids; D011506:Proteins; C025946:3-methyladenine; D000255:Adenosine Triphosphate; D000225:Adenine