Effect of ionizing radiation exposure on Trypanosoma cruzi ubiquitin-proteasome system

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. (C) 2017 Elsevier B.V. All rights reserved.CNPq - BrazilFAPEMIGPRONEXNewton Fund/FAPEMIGFAPESPUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim Imunol, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo, Dept Microbiol Imunol Parasitol, Sao Paulo, BrazilUniv Fed Ouro Preto, Inst Ciencias Exatas Biol, Dept Ciencias Biol & Nucleo Pesquisa Ciencias Bio, Ouro Preto, BrazilInst Carlos Chagas, FIOCRUZ, Curitiba, Parana, BrazilInst Biol Mol Parana, Curitiba, Parana, BrazilUniv Fed Sao Paulo, Dept Microbiol Imunol Parasitol, Sao Paulo, BrazilCNPq: 444334/2014-9FAPEMIG: APQ-00827-15Web of Scienc