Morphometric study of the effect of leupeptin, vinblastine, estron acetate and cycloheximide on the autophagic vacuole-lysosomal compartments in mouse seminal vesicle cells

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Abstract

Changes in the cytoplasmic volume fractions of autophagic vacuoles and lysosomes in mouse seminal vesicle cells were evaluated by morphometric analysis following administration of either one of the drugs estrone acetate, vinblastine sulphate, leupeptin, cycloheximide, or their different combinations. The treatments lasted for 2 h. Leupeptin caused a significant increase in the cytoplasmic volume fractions of lysosomes (defined as dense bodies limited by a single membrane) and autophagic vacuoles (defined as membrane-limited bodies containing recognizable fragments of cytoplasm) which became about 6 and 40 times larger, respectively, than controls. This was accompanied by a decrease in the ratio of surface to volume of lysosomes. An increase in the sizes of autophagic vacuole and lysosomal compartments (by about 3 and 10 times, respectively, as compared with controls) was observed in the estrone acetate - treated group. The shape of lysosomes became highly irregular in these animals and their surface densities did not differ significantly from those of controls. The cytoplasmic volume fraction of autophagic vacuoles was largest in the vinblastine treated animals (an increase by about 80 times, as compared with controls) in which the autophagic vacuole compartment became almost two times larger than the lysosomal one. The size of the latter did not differ significantly from that of controls. Cycloheximide did not exert any influence on the fractional volumes of autophagic vacuoles and lysosomes as compared with controls when applied alone and prevented all the mentioned changes when administered together with either of the three compounds. Based on the known or suggested effects of the compounds used here on protein degradation, we conclude that cycloheximide, vinblastine and leupeptin impair the autophagic process in the seminal vesicle cells at three different levels. Cycloheximide blocks the formation of autophagic vacuoles, thereby preventing the influx of material into the lytic system. Vinblastine impaires the fusion between the lysosomes and autophagosomes which results in an accumulation of the latter. Leupeptin slows down the intralysosomal degradation, thereby causing an expansion of the lysosomal compartment. Estrone acetate enlarges the size of autophagic vacuole and lysosomal compartments by enhancing the activity of the lysosomal system as a whole. However, when administered simultaneously in different combinations the drugs exerted some effects which could not be fully explained on this basis and need further study.

Original languageEnglish
Pages (from-to)83-93
Number of pages11
JournalVirchows Archiv B Cell Pathology Including Molecular Pathology
Volume41
Issue number1
DOIs
Publication statusPublished - Nov 1982

Fingerprint

Vinblastine
Seminal Vesicles
Cycloheximide
Vacuoles
Acetates
Lysosomes
Membranes
leupeptin
Drug Combinations
Proteolysis
Cytoplasm
Pharmaceutical Preparations

Keywords

  • Autophagy
  • Cycloheximide
  • Estrogens
  • Leupeptin
  • Vinblastine

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{526e863437a1415dbf54e3af51f42241,
title = "Morphometric study of the effect of leupeptin, vinblastine, estron acetate and cycloheximide on the autophagic vacuole-lysosomal compartments in mouse seminal vesicle cells",
abstract = "Changes in the cytoplasmic volume fractions of autophagic vacuoles and lysosomes in mouse seminal vesicle cells were evaluated by morphometric analysis following administration of either one of the drugs estrone acetate, vinblastine sulphate, leupeptin, cycloheximide, or their different combinations. The treatments lasted for 2 h. Leupeptin caused a significant increase in the cytoplasmic volume fractions of lysosomes (defined as dense bodies limited by a single membrane) and autophagic vacuoles (defined as membrane-limited bodies containing recognizable fragments of cytoplasm) which became about 6 and 40 times larger, respectively, than controls. This was accompanied by a decrease in the ratio of surface to volume of lysosomes. An increase in the sizes of autophagic vacuole and lysosomal compartments (by about 3 and 10 times, respectively, as compared with controls) was observed in the estrone acetate - treated group. The shape of lysosomes became highly irregular in these animals and their surface densities did not differ significantly from those of controls. The cytoplasmic volume fraction of autophagic vacuoles was largest in the vinblastine treated animals (an increase by about 80 times, as compared with controls) in which the autophagic vacuole compartment became almost two times larger than the lysosomal one. The size of the latter did not differ significantly from that of controls. Cycloheximide did not exert any influence on the fractional volumes of autophagic vacuoles and lysosomes as compared with controls when applied alone and prevented all the mentioned changes when administered together with either of the three compounds. Based on the known or suggested effects of the compounds used here on protein degradation, we conclude that cycloheximide, vinblastine and leupeptin impair the autophagic process in the seminal vesicle cells at three different levels. Cycloheximide blocks the formation of autophagic vacuoles, thereby preventing the influx of material into the lytic system. Vinblastine impaires the fusion between the lysosomes and autophagosomes which results in an accumulation of the latter. Leupeptin slows down the intralysosomal degradation, thereby causing an expansion of the lysosomal compartment. Estrone acetate enlarges the size of autophagic vacuole and lysosomal compartments by enhancing the activity of the lysosomal system as a whole. However, when administered simultaneously in different combinations the drugs exerted some effects which could not be fully explained on this basis and need further study.",
keywords = "Autophagy, Cycloheximide, Estrogens, Leupeptin, Vinblastine",
author = "J. Kov{\'a}cs",
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N2 - Changes in the cytoplasmic volume fractions of autophagic vacuoles and lysosomes in mouse seminal vesicle cells were evaluated by morphometric analysis following administration of either one of the drugs estrone acetate, vinblastine sulphate, leupeptin, cycloheximide, or their different combinations. The treatments lasted for 2 h. Leupeptin caused a significant increase in the cytoplasmic volume fractions of lysosomes (defined as dense bodies limited by a single membrane) and autophagic vacuoles (defined as membrane-limited bodies containing recognizable fragments of cytoplasm) which became about 6 and 40 times larger, respectively, than controls. This was accompanied by a decrease in the ratio of surface to volume of lysosomes. An increase in the sizes of autophagic vacuole and lysosomal compartments (by about 3 and 10 times, respectively, as compared with controls) was observed in the estrone acetate - treated group. The shape of lysosomes became highly irregular in these animals and their surface densities did not differ significantly from those of controls. The cytoplasmic volume fraction of autophagic vacuoles was largest in the vinblastine treated animals (an increase by about 80 times, as compared with controls) in which the autophagic vacuole compartment became almost two times larger than the lysosomal one. The size of the latter did not differ significantly from that of controls. Cycloheximide did not exert any influence on the fractional volumes of autophagic vacuoles and lysosomes as compared with controls when applied alone and prevented all the mentioned changes when administered together with either of the three compounds. Based on the known or suggested effects of the compounds used here on protein degradation, we conclude that cycloheximide, vinblastine and leupeptin impair the autophagic process in the seminal vesicle cells at three different levels. Cycloheximide blocks the formation of autophagic vacuoles, thereby preventing the influx of material into the lytic system. Vinblastine impaires the fusion between the lysosomes and autophagosomes which results in an accumulation of the latter. Leupeptin slows down the intralysosomal degradation, thereby causing an expansion of the lysosomal compartment. Estrone acetate enlarges the size of autophagic vacuole and lysosomal compartments by enhancing the activity of the lysosomal system as a whole. However, when administered simultaneously in different combinations the drugs exerted some effects which could not be fully explained on this basis and need further study.

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