Time course of the quantitative changes in the autophagic-lysosomal and secretory granule compartments of murine liver cells under the influence of vinblastine

Gábor Réz, L. László, Erzsébet Fellinger, A. Kovács, J. Kovács

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 aformentioned 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 enzymecarrying 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. DNA-based specific activity of the lysosomal marker enzyme acid phosphatase did not alter significantly during the 36 h period. The volume fraction of the SGC reacted to VBL in essentially the same way as the ALC. The possible mechanisms underlying the time course of the volume changes of ALC and SGC are briefly discussed.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalVirchows Archiv B Cell Pathology Including Molecular Pathology
Volume58
Issue number1
DOIs
Publication statusPublished - Dec 1989

Fingerprint

Vinblastine
Secretory Vesicles
Liver
Injections
Acid Phosphatase
Vacuoles
Lysosomes
Electrons
DNA
Enzymes
Autophagosomes
Therapeutics

Keywords

  • Autophagy
  • Li-poprotein secretion
  • Liver
  • Lysosomes
  • Microtubules
  • Vinblastine

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{d9b6df45ea5d4e9281eb4a98b120c0af,
title = "Time course of the quantitative changes in the autophagic-lysosomal and secretory granule compartments of murine liver cells under the influence of vinblastine",
abstract = "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 aformentioned 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 enzymecarrying 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. DNA-based specific activity of the lysosomal marker enzyme acid phosphatase did not alter significantly during the 36 h period. The volume fraction of the SGC reacted to VBL in essentially the same way as the ALC. The possible mechanisms underlying the time course of the volume changes of ALC and SGC are briefly discussed.",
keywords = "Autophagy, Li-poprotein secretion, Liver, Lysosomes, Microtubules, Vinblastine",
author = "G{\'a}bor R{\'e}z and L. L{\'a}szl{\'o} and Erzs{\'e}bet Fellinger and A. Kov{\'a}cs and J. Kov{\'a}cs",
year = "1989",
month = "12",
doi = "10.1007/BF02890071",
language = "English",
volume = "58",
pages = "189--197",
journal = "Virchows Archiv B Cell Pathology Including Molecular Pathology",
issn = "0042-6431",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Time course of the quantitative changes in the autophagic-lysosomal and secretory granule compartments of murine liver cells under the influence of vinblastine

AU - Réz, Gábor

AU - László, L.

AU - Fellinger, Erzsébet

AU - Kovács, A.

AU - Kovács, J.

PY - 1989/12

Y1 - 1989/12

N2 - 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 aformentioned 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 enzymecarrying 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. DNA-based specific activity of the lysosomal marker enzyme acid phosphatase did not alter significantly during the 36 h period. The volume fraction of the SGC reacted to VBL in essentially the same way as the ALC. The possible mechanisms underlying the time course of the volume changes of ALC and SGC are briefly discussed.

AB - 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 aformentioned 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 enzymecarrying 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. DNA-based specific activity of the lysosomal marker enzyme acid phosphatase did not alter significantly during the 36 h period. The volume fraction of the SGC reacted to VBL in essentially the same way as the ALC. The possible mechanisms underlying the time course of the volume changes of ALC and SGC are briefly discussed.

KW - Autophagy

KW - Li-poprotein secretion

KW - Liver

KW - Lysosomes

KW - Microtubules

KW - Vinblastine

UR - http://www.scopus.com/inward/record.url?scp=0025189643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025189643&partnerID=8YFLogxK

U2 - 10.1007/BF02890071

DO - 10.1007/BF02890071

M3 - Article

C2 - 1970680

AN - SCOPUS:0025189643

VL - 58

SP - 189

EP - 197

JO - Virchows Archiv B Cell Pathology Including Molecular Pathology

JF - Virchows Archiv B Cell Pathology Including Molecular Pathology

SN - 0042-6431

IS - 1

ER -