| Texto completo | |
| Autor(es): |
dos Santos Moura, Leila
[1, 2]
;
Santana Nunes, Vinicius
[2]
;
Gomes, Antoniel A. S.
[3]
;
Sousa, Ana Caroline de Castro Nascimento
[1, 2]
;
Fontes, Marcos R. M.
[3]
;
Schenkman, Sergio
[1]
;
Moretti, Nilmar Silvio
[1, 2]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Lab Biol Mol Patogenos, Escola Paulista Med, Sao Paulo - Brazil
[3] Univ Estadual Paulista, Inst Biociencias, Dept Biofis & Farmacol, Botucatu, SP - Brazil
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 11, NOV 11 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
Trypanosoma cruzi faces a variety of environmental scenarios during its life cycle, which include changes in the redox environment that requires a fine regulation of a complex antioxidant arsenal of enzymes. Reversible posttranslational modifications, as lysine acetylation, are a fast and economical way for cells to react to environmental conditions. Recently, we found that the main antioxidant enzymes, including the mitochondrial superoxide dismutase A (TcSODA) are acetylated in T. cruzi, suggesting that protein acetylation could participate in the oxidative stress response in T. cruzi. Therefore, we investigated whether mitochondrial lysine deacetylase TcSir2rp3 was involved in the activity control of TcSODA. We observed an increased resistance to hydrogen peroxide and menadione in parasites overexpressing TcSir2rp3. Increased resistance was also found for benznidazole and nifurtimox, known to induce reactive oxidative and nitrosactive species in the parasite, associated to that a reduction in the ROS levels was observed. To better understand the way TcSir2rp3 could contributes to oxidative stress response, we analyzed the expression of TcSODA in the TcSir2rp3 overexpressing parasites and did not detect any increase in protein levels of this enzyme. However, we found that these parasites presented higher levels of superoxide dismutase activity, and also that TcSir2rp3 and TcSODA interacts in vivo. Knowing that TcSODA is acetylated at lysine residues K44 and K97, and that K97 is located at a similar region in the protein structure as K68 in human manganese superoxide dismutase (MnSOD), responsible for regulating MnSOD activity, we generated mutated versions of TcSODA at K44 and K97 and found that replacing K97 by glutamine, which mimics an acetylated lysine, negatively affects the enzyme activity in vitro. By using molecular dynamics approaches, we revealed that acetylation of K97 induces specific conformational changes in TcSODA with respect to hydrogen-bonding pattern to neighbor residues, suggesting a key participation of this residue to modulate the affinity to O2- . Taken together, our results showed for the first time the involvement of lysine acetylation in the maintenance of homeostatic redox state in trypanosomatids, contributing to the understanding of mechanisms used by T. cruzi to progress during the infection. (AU) | |
| Processo FAPESP: | 14/03714-7 - Interação da proteína Sir2 com fatores de início de tradução em Trypanosoma |
| Beneficiário: | Vinícius Santana Nunes |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 20/07870-4 - Mecanismos de adaptação de tripanossomatídeos ao hospedeiro através de controle da transcrição, síntese proteica e secreção de vesículas extracelulares |
| Beneficiário: | Ana Claudia Trocoli Torrecilhas |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 18/09948-0 - Estudo da acetilação proteica em Leishmania |
| Beneficiário: | Nilmar Silvio Moretti |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 15/22031-0 - Sinalização celular em Trypanosoma durante a interação do parasita com o hospedeiro |
| Beneficiário: | Sergio Schenkman |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 12/09403-8 - Estudo do papel das modificações de cromatina nos mecanismos de reparo de dano no DNA e controle da transcrição em Trypanosoma |
| Beneficiário: | Nilmar Silvio Moretti |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |