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Type: Artigo
Title: Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1(142)-macrophages
Author: Barbosa, Guilherme O.
Silva, Juliete A. F.
Siqueira-Berti, Aline
Nishan, Umar
Rosa-Ribeiro, Rafaela
Oliveira, Silvia B. P.
Baratti, Mariana O.
Ferrucci, Danilo
Santana, Julio C. O.
Damas-Souza, Danilo M.
Bruni-Cardoso, Alexandre
Augusto, Taize M.
Correa-da-Silva, Felipe
Moraes-Vieira, Pedro M.
Stach-Machado, Dagmar R.
Felisbino, Sergio L.
Menezes, Gustavo B.
Cesarz, Carlos L.
Carvalho, Hernandes F.
Abstract: Prostate development and function are regulated by androgens. Epithelial cell apoptosis in response to androgen deprivation is caspase-9-dependent and peaks at Day 3 after castration. However, isolated epithelial cells survive in the absence of androgens. Znf142 showed an on-off expression pattern in intraepithelial CD68-positive macrophages, with the on-phase at Day 3 after castration. Rats treated with gadolinium chloride to deplete macrophages showed a significant drop in apoptosis, suggesting a causal relationship between macrophages and epithelial cell apoptosis. Intraepithelial M1-polarization was also limited to Day 3, and the inducible nitric oxide synthase (iNOS) knockout mice showed significantly less apoptosis than wild-type controls. The epithelial cells showed focal DNA double-strand breaks (DSB), 8-oxoguanine, and protein tyrosine-nitrosylation, fingerprints of exposure to peroxinitrite. Cultured epithelial cells induced M1-polarization and showed focal DSB and underwent apoptosis. The same phenomena were reproduced in LNCaP cells cocultured with Raw 264.7 macrophages. In conclusion, the M1 (142)-macrophage (named after Znf142) attack causes activation of the intrinsic apoptosis pathway in epithelial cells after castration
Subject: Apoptose
Células epiteliais
Country: Estados Unidos
Editor: John Wiley & Sons
Rights: Fechado
Identifier DOI: 10.1002/jcp.28544
Date Issue: 2019
Appears in Collections:IB - Artigos e Outros Documentos

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