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The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and induces an irreversible pseudocystic transformation and cell death in Tritrichomonas foetus
- Source :
- Parasitology Research. 115:3057-3069
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Proteasomal proteolysis is required for a wide range of cellular processes, including protein quality control, cell cycle progression, cell death and metabolic adaptation to environment changes or stress responses. Proteasome inhibitors are useful compounds for determining the roles of proteasome in eukaryotic cells. Here, we investigated the effects of gliotoxin, a proteasome inhibitor, on the cell growth, replication, ultrastructure, DNA integrity and proteasomal proteolytic activity of the protist parasite Tritrichomonas foetus. The effect of gliotoxin on the transformation of T. foetus to endoflagellar form (EFF), also known as pseudocyst, was investigated. Gliotoxin inhibited the culture growth, arrested cell cycle, and provoked a trichomonacidal effect in a dose-dependent manner. Parasites treated with gliotoxin displayed features typical of cell death, such as membrane blebbing, concentric membrane whorls containing remnants of organelles, intense cytosolic and nuclear vacuolisation, chromatin condensation, DNA fragmentation, cytoplasmic disintegration and plasma membrane disruption. The proteasomal peptidase activity was inhibited by gliotoxin in a dose-dependent manner. Gliotoxin treatment also induced an irreversible EFF transformation in a dose/time-dependent manner. We compared morphological characteristics between gliotoxin- and cold-induced EFF parasites. Our results suggest that gliotoxin could induce EFF transformation by a mechanism distinct from that provoked by cold temperature. This study further contributes to a better understanding of the role of proteasome system in cell cycle, cell death and EFF transformation in T. foetus.
- Subjects :
- 0301 basic medicine
Proteasome Endopeptidase Complex
Programmed cell death
Cell cycle checkpoint
030106 microbiology
Apoptosis
DNA Fragmentation
Tritrichomonas foetus
Biology
03 medical and health sciences
chemistry.chemical_compound
Gliotoxin
medicine
Animals
Cell Proliferation
Cell Death
General Veterinary
Cell growth
Cell Cycle
Cell Cycle Checkpoints
General Medicine
Cell cycle
Cell biology
030104 developmental biology
Infectious Diseases
chemistry
Biochemistry
Proteasome
Insect Science
Proteolysis
Proteasome inhibitor
Parasitology
Proteasome Inhibitors
medicine.drug
Subjects
Details
- ISSN :
- 14321955 and 09320113
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Parasitology Research
- Accession number :
- edsair.doi.dedup.....f095e7910eb102c2bdbae22e7cc74a50