NDLI: The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and induces an irreversible pseudocystic transformation and cell death in Tritrichomonas foetus

Content Provider	Springer Nature Link
Author	Pereira Neves, Antonio Menna Barreto, Rubem F. S. Benchimol, Marlene
Copyright Year	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.
Starting Page	3057
Ending Page	3069
Page Count	13
File Format	PDF
ISSN	09320113
Journal	Parasitology Research
Volume Number	115
Issue Number	8
e-ISSN	14321955
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-04-23
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell replication Electron microscopy Endoflagellar form Proteasome inhibitor Trichomonosis Medical Microbiology Microbiology Immunology
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Veterinary Parasitology Insect Science

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