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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Pep5, a Fragment of Cyclin D2, Shows Antiparasitic Effects in Different Stages of the Trypanosoma cruzi Life Cycle and Blocks Parasite Infectivity

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de Araujo, Christiane Bezerra [1, 2] ; de Lima, Loyze Paola [1, 2] ; Calderano, Simone Guedes [3] ; Damasceno, Flavia Silva [4] ; Silber, Ariel M. [4] ; Elias, Maria Carolina [1, 2]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Inst Butantan, Lab Especial Ciclo Celular, Sao Paulo - Brazil
[2] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Sao Paulo - Brazil
[3] Inst Butantan, Lab Parasitol, Sao Paulo - Brazil
[4] Inst Ciencias Biomed, Dept Parasitol, Lab Biochem Tryps LaBTryps, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Antimicrobial Agents and Chemotherapy; v. 63, n. 5 MAY 2019.
Citações Web of Science: 2

Pep5 (WELVVLGKL) is a fragment of cyclin D2 that exhibits a 2-fold increase in the S phase of the HeLa cell cycle. When covalently bound to a cell-penetrating peptide (Pep5-cpp), the nonapeptide induces cell death in several tumor cells, including breast cancer and melanoma cells. Additionally, Pep5-cpp reduces the in vivo tumor volume of rat glioblastoma. Chagas disease, which is caused by the flagellated parasite Trypanosoma cruzi, is a neglected disease that occurs mainly in the Americas, where it is considered an important public health issue. Given that there are only two options for treating the disease, it is exceptionally crucial to search for new molecules with potential pharmacological action against the parasites. In this study, we demonstrate that Pep5-cpp induces cell death in epimastigote, trypomastigote, and amastigote forms of T. cruzi. The Pep5-cpp peptide was also able to decrease the percentage of infected cells without causing any detectable toxic effects in mammalian host cells. The infective, i.e., trypomastigote form of T. cruzi pretreated with Pep5-cpp was unable to infect LLC-MK2 monkey kidney cells. Also, Pep5-binding proteins were identified by mass spectrometry, including calmodulin-ubiquitin-associated protein, which is related to the virulence and parasitemia of T. cruzi. Taken together, these data suggest that Pep5 can be used as a novel alternative for the treatment of Chagas disease. (AU)

Processo FAPESP: 16/50050-2 - How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites?
Beneficiário:Maria Carolina Quartim Barbosa Elias Sabbaga
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/06034-2 - O papel biológico de aminoácidos e seus metabólitos derivados em Trypanosoma cruzi
Beneficiário:Ariel Mariano Silber
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/13375-5 - Origens da replicação em tripanossomas
Beneficiário:Christiane Bezerra de Araujo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
Beneficiário:Hugo Aguirre Armelin
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 17/16553-0 - O papel das isoformas mitocondrial e glicossomal da fumarato redutase na bioenergética de Trypanosoma cruzi
Beneficiário:Ariel Mariano Silber
Linha de fomento: Auxílio à Pesquisa - Pesquisador Visitante - Internacional