Pentachloropseudilin Impairs Angiogenesis by Disrupting the Actin Cytoskeleton, Integrin Trafficking and the Cell Cycle

Autor(es):Mostrar menos -

Teixeira, Samuel Cota ^[1] ; Lopes, Daiana Silva ^[2] ; da Silva, Marcelo Santos ^{[3, 4]} ; Cordero da Luz, Felipe Andres ^[1] ; Cirilo Gimenes, Sarah Natalie ^[5] ; Borges, Bruna Cristina ^[1] ; da Silva, Aline Alves ^[1] ; Martins, Flavia Alves ^[1] ; dos Santos, Marius Alves ^[1] ; Teixeira, Thaise Lara ^[1] ; Oliveira, Ricardo A. ^[6] ; Rodrigues Avila, Veridiana de Melo ^[7] ; Barbosa Silva, Marcelo Jose ^[1] ; Elias, Maria Carolina ^[3] ; Martin, Rene ^[8] ; da Silva, Claudio Vieira ^[1] ; Knoelker, Hans-Joachim ^[8]

Afiliação do(s) autor(es)

^[1] Univ Fed Uberlandia, Dept Immunol, Biomed Sci Inst, Rua Piaui, Bloco 2B, Sala 200, Campus Umuarama, BR-38400902 Uberlandia, MG - Brazil

^[2] Univ Fed Bahia, Multidisciplinary Inst Hlth, Anisio Teixeira Campus, Rua Hormindo Barros 58, BR-45029094 Vitoria Da Conquista, BA - Brazil

^[3] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, Special Lab Cell Cycle LECC, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[4] Univ Glasgow, Inst Infect Immun & Inflammat, Wellcome Ctr Mol Parasitol, Sir Graeme Davies Bldg, 120 Univ Pl, Glasgow G12 8TA, Lanark - Scotland

^[5] Butantan Inst, Imunopathol Lab, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[6] Univ Fed Uberlandia, Med Sch, Av Para, Bloco 2u, 1720 Umuarama, BR-38400902 Uberlandia, MG - Brazil

^[7] Univ Fed Uberlandia, Inst Biotechnol, Av Para, 1720, Bloco 2E, Salas 246, Campus Umuarama, BR-38405320 Uberlandia, MG - Brazil

^[8] Tech Univ Dresden, Fak Chem, Bergstr 66, D-01069 Dresden - Germany

• Tipo de documento: Artigo Científico
• Fonte: CHEMBIOCHEM; v. 20, n. 18 AUG 2019.
• Citações Web of Science: 0

Resumo

Class 1 myosins (Myo1s) were the first unconventional myosins identified and humans have eight known Myo1 isoforms. The Myo1 family is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1s in different biological processes is evident. In this study, we have investigated the effects of pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1s, on angiogenesis. We demonstrated that treatment of cells with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely to be related to the inhibition of cell proliferation, migration and adhesion, as well as to alteration of the actin cytoskeleton pattern, as shown on a PClP-treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that PClP caused DNA strand breaks, which are probably repaired during the cell cycle arrest in the G1 phase. Taken together, our results suggest that Myo1s participate directly in the angiogenesis process. (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: 14/24170-5 - Dinâmica da replicação do DNA em Trypanosoma cruzi: caracterização do licenciamento e da taxa de replicação
• Beneficiário: Marcelo Santos da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado