Betulinic Acid Exerts Cytoprotective Activity on Zika Virus-Infected Neural Progenitor Cells.

Autor:	Cavalcante BRR; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Aragão-França LS; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Sampaio GLA; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Nonaka CKV; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Oliveira MS; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Campos GS; Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Sardi SI; Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Dias BRS; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Menezes JPB; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Rocha VPC; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Rossi EA; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Paredes BD; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Martins GLS; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Allahdadi KJ; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Peixoto LR; Department of Pharmacy, Federal University of Paraíba, João Pessoa, Brazil., Barbosa-Filho JM; Department of Pharmacy, Federal University of Paraíba, João Pessoa, Brazil., Souza BSF; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil., Soares MBP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2020 Nov 05; Vol. 10, pp. 558324. Date of Electronic Publication: 2020 Nov 05 (Print Publication: 2020).
DOI:	10.3389/fcimb.2020.558324
Abstrakt:	Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2 + NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2 + and Casp3 + NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs. (Copyright © 2020 Cavalcante, Aragão-França, Sampaio, Nonaka, Oliveira, Campos, Sardi, Dias, Menezes, Rocha, Rossi, Paredes, Martins, Allahdadi, Peixoto, Barbosa-Filho, Souza and Soares.)
Databáze:	MEDLINE
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