Actin-depolymerization factor (NcADF): oxidation as regulator of NcADF activity on programmed cell death of Neospora caninum

• Grant number: 18/21020-3
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2018
• End date: August 31, 2021
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
• Principal Investigator: Ana Patricia Yatsuda Natsui
• Grantee: Ana Patricia Yatsuda Natsui
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Luciana Baroni ; Luiz Miguel Pereira

Abstract

Neospora caninum (Nc) is an obligatory intracellular parasite that belongs to the Phylum Apicomplexa. It is the etiological agent of neosporosis, a treatment-challenging disease that causes abortion in cattle. The economic losses caused to cattle industry by neosporosis, associated to the absence of treatment to control this parasitic disease, spotlights Nc as an important investigation target toward development of therapeutic strategies. The investigation of molecular mechanisms responsible for parasites survival and dissemination may reveal targets for therapeutic approaches. The ADF/cofilin family is known to be responsible for actin dynamics modulation and exhibits versatility in cellular functions. Oxidized mammalian cofilins mediate apoptosis by their translocation into mitochondria and release of cytochrome c. However, this mechanism is not uncovered in protozoan cells. Apoptosis is a process of programmed cell death that has been studied in protozoans due to its peculiar mechanistic characteristics compared to metazoans. Based on that, we aim at investigating the role of oxidation as a regulator factor of N. caninum ADF (NcADF) and evaluating the possible association of oxidized NcADF and apoptosis-like signaling pathway. The protein oxidation will be induced by N-chlorotaurine (TnCl), an antimicrobial substance, which is produced by neutrophils. Due to the unknown effect in apicomplexans, TnCl will be tested in Nc tachyzoites and the oxidative stress and programmed cell death induction will be investigated. In parallel, the oxidized residues will be determined in recombinant NcADF, as well as the role of oxidized NcADF in actin dynamics. After confirmation of NcADF oxidation evidences, the recombinant protein will have its capacity to mitochondrial translocation investigated in isolated N. caninum mitochondrion. The confirmation of the hypothesis that oxidized NcADF participates on Nc programmed cell death may contribute significantly to the comprehension of important cellular processes for parasitic survival, encouraging the future development of therapeutic intervention strategies. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VENANCIO-BROCHI, JADE CABESTRE; PEREIRA, LUIZ MIGUEL; CALIL, FELIPE ANTUNES; TEIXEIRA, OLIVIA; BARONI, LUCIANA; ABREU-FILHO, PERICLES GAMA; BRAGA, GILBERTO UBIDA LEITE; NONATO, MARIA CRISTINA; YATSUDA, ANA PATRICIA. Glutathione reductase: A cytoplasmic antioxidant enzyme and a potential target for phenothiazinium dyes in Neospora caninum. International Journal of Biological Macromolecules, v. 187, p. 964-975, SEP 30 2021. (19/05758-5, 18/21020-3)

VENANCIO-BROCHI, JADE CABESTRE; PEREIRA, LUIZ MIGUEL; BARONI, LUCIANA; ABREU-FILHO, PERICLES GAMA; YATSUDA, ANA PATRICIA. Characterization of the Neospora caninum peroxiredoxin: a novel peroxidase and antioxidant enzyme. Parasitology Research, v. 121, n. 6, p. 14-pg., 2022-04-01. (18/21020-3, 19/05758-5)

POSSATO, BRUNA; DALMOLIN, LUCIANA FALCCO; PEREIRA, LUIZ MIGUEL; ALVES, JACQUELINE QUERINO; SILVA, RAPHAEL TRISTAO CRUVINEL; GELAMO, ROGERIO VALENTIM; YATSUDA, ANA PATRICIA; LOPEZ, RENATA FONSECA VIANNA; DE ALBUQUERQUE, SERGIO; LEITE, NATALIA BUENO; et al. Gold(III) complexes with thiosemicarbazonate ligands as potential anticancer agents: Cytotoxicity and interactions with biomolecular targets. European Journal of Pharmaceutical Sciences, v. 162, JUL 1 2021. (18/21020-3, 18/10711-5, 18/24544-3)

PEREIRA, LUIZ MIGUEL; PORTAPILLA, GISELE BULHOES; BRANCINI, GUILHERME THOMAZ PEREIRA; POSSATO, BRUNA; DA COSTA, CASSIA MARIANA BRONZON; ABREU-FILHO, PERICLES GAMA; WAINWRIGHT, MARK; YATSUDA, ANA PATRICIA; BRAGA, GILBERTO UBIDA LEITE. The potential of phenothiazinium dyes as cytotoxicity markers in cisplatin-treated cells. SCIENTIFIC REPORTS, v. 13, n. 1, p. 17-pg., 2023-06-23. (18/21020-3, 17/17579-2, 18/10711-5, 16/11386-5)