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

Autor(es)

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]}

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

• Tipo de documento: Artigo Científico
• Fonte: Antimicrobial Agents and Chemotherapy; v. 63, n. 5 MAY 2019.
• Citações Web of Science: 2

Resumo

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: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/06034-2 - O papel biológico de aminoácidos e seus metabólitos derivados em Trypanosoma cruzi
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/16553-0 - O papel das isoformas mitocondrial e glicossomal da fumarato redutase na bioenergética de Trypanosoma cruzi
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional
• 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
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/13375-5 - Origens da replicação em tripanossomas
• Beneficiário: Christiane Bezerra de Araujo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado