Time course of the quantitative changes in the autophagic-lysosomal and secretory granule compartments of murine liver cells under the influence of vinblastine.
The dynamics of the transient expansion of the autophagic-lysosomal (ALC) and secretory granule (SGC) compartments in mouse liver cells were monitored by electron microscopic morphometry after a single injection of 10 mg/kg b.w. vinblastine sulfate (VBL). Initially (first phase) the cytoplasmic volume fractions of the total ALC and its subcompartments, as well as of the SGC increased by an order of magnitude and peaked at the second h. In the second phase, all the aforementioned compartments regressed gradually, approaching their normal size between 12 and 36 h after VBL injection. Analysis of the dynamic changes in fractional volumes of subcompartments of the ALC showed that early autophagic vacuoles (AV1) were the first to enlarge. Advanced AVs (AV2) reacted 30 min later and a further 30 min time lag was required before late autolysosomes, appearing as dense bodies (DB), started to expand. We regard these data as kinetic proof that the bodies of the later reacting subcompartments developed from the earlier reacting ones. The time lag between the expansion of AV1 and AV2 subcompartments may be explained by a period of retardation of conversion of nascent autophagosomes (AV1) to autolysosomes (AV2) which is known to occur normally by fusion of AV1 with enzyme-carrying lysosomes. However, transformation of AV1 to AV2 and later to DB resumed after the respective time lags. Moreover, our quantitative data lend support to the view that segregation of cytoplasmic portions into newly-formed autophagosomes was stimulated by VBL, at least in the first 2 h of treatment. The expansion of ALC accelerated during this period and led to an obvious overload of the lysosomal apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)
Réz
G
G
Department of General Zoology, Eötvös University, Budapest, Hungary.
Lászlò
L
L
Fellinger
E
E
Kovács
A L
AL
Kovács
J
J
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002451:Cell Compartmentation / Q000187:drug effects*; D003594:Cytoplasmic Granules / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000187:drug effects*; D013997:Time Factors; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine