title: Effect of ionizing radiation exposure on Trypanosoma cruzi ubiquitin-proteasome system.
abstract: In recent years, proteasome involvement in the damage response induced by ionizing radiation (IR) became evident. However, whether proteasome plays a direct or indirect role in IR-induced damage response still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance to IR, suggesting a highly efficient damage response system. Here, we investigate the role of T. cruzi proteasome in the damage response induced by IR. We exposed epimastigotes to high doses of gamma ray and we analyzed the expression and subcellular localization of several components of the ubiquitin-proteasome system. We show that proteasome inhibition increases IR-induced cell growth arrest and proteasome-mediated proteolysis is altered after parasite exposure. We observed nuclear accumulation of 19S and 20S proteasome subunits in response to IR treatments. Intriguingly, the dynamic of 19S particle nuclear accumulation was more similar to the dynamic observed for Rad51 nuclear translocation than the observed for 20S. In the other hand, 20S increase and nuclear translocation could be related with an increase of its regulator PA26 and high levels of proteasome-mediated proteolysis in vitro. The intersection between the opposed peaks of 19S and 20S protein levels was marked by nuclear accumulation of both 20S and 19S together with Ubiquitin, suggesting a role of ubiquitin-proteasome system in the nuclear protein turnover at the time. Our results revealed the importance of proteasome-mediated proteolysis in T. cruzi IR-induced damage response suggesting that proteasome is also involved in T. cruzi IR tolerance. Moreover, our data support the possible direct/signaling role of 19S in DNA damage repair. Based on these results, we speculate that spatial and temporal differences between the 19S particle and 20S proteasome controls proteasome multiple roles in IR damage response.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Paula G
authors.initials: PG
authors.lastname: Cerqueira
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Passos-Silva
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: João P
authors.initials: JP
authors.lastname: Vieira-da-Rocha
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Isabela Cecilia
authors.initials: IC
authors.lastname: Mendes
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Karla A
authors.initials: KA
authors.lastname: de Oliveira
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Camila F B
authors.initials: CF
authors.lastname: Oliveira
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Liza F F
authors.initials: LF
authors.lastname: Vilela
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ronaldo A P
authors.initials: RA
authors.lastname: Nagem
authors.affiliation: Instituto Carlos Chagas, Fiocruz, Curitiba, Paraná, Brazil.
authors.forename: Joseane
authors.initials: J
authors.lastname: Cardoso
authors.affiliation: Instituto Carlos Chagas, Fiocruz, Curitiba, Paraná, Brazil.
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Nardelli
authors.affiliation: Instituto de Biologia Molecular do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Krieger
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Glória R
authors.initials: GR
authors.lastname: Franco
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Macedo
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sérgio D J
authors.initials: SD
authors.lastname: Pena
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Schenkman
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Dawidson A
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Departamento de Ciências Biológicas & Núcleo de Pesquisa em Ciências Biológicas, Instituto de Ciências Exatas e Biológica, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Guerra-Sá
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: crmachad@icb.ufmg.br.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Machado
mesh_terms: D004260:DNA Repair; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D011839:Radiation, Ionizing; D014349:Trypanosoma cruzi / Q000378:metabolism* / Q000528:radiation effects*; D025801:Ubiquitin / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Ionizing radiation; Proteasome; Trypanosoma cruzi