Show simple item record

dc.contributor.authorMoura, Leila dos Santos [UNIFESP]
dc.contributor.authorNunes, Vinícius Santana [UNIFESP]
dc.contributor.authorGomes, Antoniel A. S.
dc.contributor.authorSousa, Ana Caroline de Castro Nascimento [UNIFESP]
dc.contributor.authorFontes, Marcos R. M.
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.authorMoretti, Nilmar Silvio [UNIFESP]
dc.date.accessioned2021-11-29T17:02:20Z
dc.date.available2021-11-29T17:02:20Z
dc.date.issued2021
dc.identifier.urihttps://repositorio.unifesp.br/xmlui/handle/11600/62331
dc.description.abstractTrypanosoma cruzi faces a variety of environmental scenarios during its life cycle, which include changes in the redox environment that requires a !ne regulation of a complex antioxidant arsenal of enzymes. Reversible posttranslational modi!cations, 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 speci!c conformational changes in TcSODA with respect to hydrogen-bonding pattern to neighbor residues,suggesting a key participation of this residue to modulate the af!nity to O!2. Taken together, our results showed for the !rst 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.pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.languageengpt_BR
dc.publisherFrontierspt_BR
dc.relation.ispartofFrontiers in Cellular and Infection Microbiologypt_BR
dc.rightsAcesso abertopt_BR
dc.subjectTrypanosoma cruzipt_BR
dc.subjectAcetylationpt_BR
dc.subjectSuperoxide dismutasept_BR
dc.subjectSirtuinspt_BR
dc.subjectOxidative stresspt_BR
dc.titleMitochondrial sirtuin TcSir2rp3 affects TcSODA activity and oxidative stress response in Trypanosoma cruzipt_BR
dc.typeArtigopt_BR
dc.description.sponsorshipIDFAPESP: 2018/09948-0pt_BR
dc.description.sponsorshipIDCNPq: 424729/2018pt_BR
dc.identifier.doi10.3389/fcimb.2021.773410pt_BR
unifesp.campusEscola Paulista de Medicina (EPM)pt_BR
unifesp.graduateProgramMicrobiologia e Imunologiapt_BR
unifesp.knowledgeAreaOutrapt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/2131472726202687pt_BR
unifesp.departamentoMicrobiologia, Imunologia e Parasitologiapt_BR


Files in this item

This item appears in the following Collection(s)

Show simple item record