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2030-01-01
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- IOC - Artigos de Periódicos [12973]
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THE FUNGAL METABOLITE GLIOTOXIN INHIBITS PROTEASOME PROTEOLYTIC ACTIVITY AND INDUCES AN IRREVERSIBLE PSEUDOCYSTIC TRANSFORMATION AND CELL DEATH IN TRITRICHOMONAS FOETUS
Microscopia eletrônica
Inibidor de proteassoma
Tritrichomonas foetus
Pseudocisto Pancreático
Electron microscopy
Endoflagellar form
Proteasome inhibitor
Tritrichomonas foetus
pseudocyst
Affilliation
Fiocruz Pernambuco. Centro de Pesquisa Aggeu Magalhães. Departamento de Microbiologia. Recife, PE, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil / UNIGRANRIO. Universidade do Grande Rio. Duque de Caxias, RJ, Brasil / Universidade Federal do Rio de Janeiro Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil / UNIGRANRIO. Universidade do Grande Rio. Duque de Caxias, RJ, Brasil / Universidade Federal do Rio de Janeiro Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
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,
DNAintegrity 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.
Keywords in Portuguese
Replicação celularMicroscopia eletrônica
Inibidor de proteassoma
Tritrichomonas foetus
Pseudocisto Pancreático
Keywords
Cell replicationElectron microscopy
Endoflagellar form
Proteasome inhibitor
Tritrichomonas foetus
pseudocyst
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