Time course of vinblastine-induced cellular autophagy in the murine pancreatic acinar cells in vivo. Different regression rates of the autophagic compartment caused by cycloheximide given different times after the vinca alkaloid. A morphometric study.
Autophagy is a three-step process in which parts of cytoplasm are segregated by membranes to form autophagosomes gaining acid hydrolases later, being converted this way into autolysosomes in which lysosomal degradation takes place. The actual size of the autophagic vacuole compartment (AVC) is obviously dependent on the velocity of these main steps. According to our morphometric measurements, a single dose (10 mg/kg b.wt.) of vinblastine (VBL) caused a conspicuous expansion of the AVC in pancreatic acinar cells, occurring in two waves: it expanded in the first 90 min but regressed in the next hour. This was followed by a second expansion monitored until the 5th post-injectional hour. The expansion rates indicate the existence of stimulation of autophagic segregation in both expansion phases. To take a further look, into the dynamics of the process, we blocked segregation by giving cycloheximide (CHI 0.2 mg/g b.wt.) 1 and 3 h after VBL and the subsequent regression of the AVC was followed by morphometry in the next 90 min. At the height of the first wave (1-2 h after VBL) the regression of AVC was not retarded, but rather, degradation rate seemed elevated. When CHI was given 1 h after VBL, 92% of the cytoplasmic volume fraction (CVF) of AVC regressed within the next 30 min. The main factor causing the expansion of AVC might be enhanced segregation in the first wave. Contrarily, at the beginning of the second wave, the turnover of AVs is dramatically slowed down. When CHI was given 3 h after VBL, only 27% of CVF of AVC regressed in the next 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Oliva
O
O
Department of General Zoology, Eötvös Loránd University, Budapest, Hungary.
Réz
G
G
Pálfia
Z
Z
Fellinger
E
E
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002462:Cell Membrane / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000648:ultrastructure; D013997:Time Factors; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine; D003513:Cycloheximide