Translational inhibitors cycloheximide, emetine, and puromycin inhibit cellular autophagy in mouse liver parenchymal and pancreatic acinar cells in vivo.
The protein synthesis inhibitor cycloheximide is widely used (in vitro or in vivo) to inhibit the autophagic degradation of endogenous cellular proteins. Circumstantial evidence has been obtained largely from in vitro experiments for a similar effect of other translational inhibitors. In the present study, the in vivo effects of cycloheximide, emetine and puromycin on autophagy in murine exocrine pancreatic and liver cells were tested using electron microscopic morphometry. The experiments were based on the assumption that the autophagic compartment will regress if the formation of the vacuoles is blocked while degradation in the pre-existing vacuoles goes on. To make the measurements easier, autophagic compartment of the cells was greatly enlarged in both cell types by administering vinblastine (10 mg/kg b. wt.) for 2 h when the inhibitors were set on for an additional 30 min. During this half-an-hour, cycloheximide (0.2 mg/g b. wt.), emetine (0.12 mg/g b. wt.) and puromycin (0.2 mg/g b. wt.), respectively caused 58.5, 35.6, and 69.5% regression of the pancreatic and 46.7, 64.2, and 54.2% of the hepatocytic autophagic vacuole compartment. Thus, similarly to cycloheximide, both emetine and puromycin have proved to be inhibitors of autophagy in vivo. The results argue for a possible relationship between the synthesis and degradation of endogenous cellular proteins.
Oliva
O
O
Dept. of General Zoology, Eötvös Univ. Budapest, Hungary.
László
L
L
Pálfia
Z
Z
Réz
G
G
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D011691:Puromycin; D014747:Vinblastine; D003513:Cycloheximide; D004640:Emetine