Occurrence and inhibition by cycloheximide of apoptosis in vinblastine-treated murine pancreas. A role for autophagy?
While investigating the time course of the influence of autophagy-inducer vinblastine in pancreatic acinar cells, we discovered that about 24 h after the single injection of the drug (10 mg/kg b.wt.) when most of the cells were already recovering from the autophagic wave, dying cells with apoptotic nuclei and peculiar morphology of their cytoplasm appeared in the exocrine pancreas. Apoptotic blebs (ABs) separating from apoptotic cells or already phagocytized by neighbouring cells were also also observed. A large number of autophagic vacuoles (AVs) were seen in these cells termed apoptotic cell (AC). They are most probably derived from cells with morphologically normal nuclei but with unusually high number of AVs in their cytoplasm. We termed these cells highly autophagic cells (HAC). Our morphometric measurements show that the partial volume of both HAC and AC increased to 7.5 and 9.5%, respectively, of total cellular volume in the 25th h after vinblastine treatment. This increase could be inhibited by a treatment at the 24th h with cycloheximide (0.2 mg/g b.wt.) an inhibitor of both translation and autophagic segregation. Thus, synthesis of proteins or an enhanced autophagy may be indispensable step(s) in the apoptotic process in this system.
Réz
G
G
Department of General Zoology, Eötvös Loránd University, Budapest, Hungary.
Pálfia
Z
Z
Fellinger
E
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine; D003513:Cycloheximide