Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1(142)-macrophages

Author(s):Show less -

Barbosa, Guilherme O. ^[1] ; Silva, Juliete A. F. ^[1] ; Siqueira-Berti, Aline ^[1] ; Nishan, Umar ^[1] ; Rosa-Ribeiro, Rafaela ^[1] ; Oliveira, Silvia B. P. ^[1] ; Baratti, Mariana O. ^{[2, 1]} ; Ferrucci, Danilo ^[1] ; Santana, Julio C. O. ^[1] ; Damas-Souza, Danilo M. ^[1] ; Bruni-Cardoso, Alexandre ^[3] ; Augusto, Taize M. ^[4] ; Correa-da-Silva, Felipe ^[5] ; Moraes-Vieira, Pedro M. ^[5] ; Stach-Machado, Dagmar R. ^[1] ; Felisbino, Sergio L. ^{[2, 6]} ; Menezes, Gustavo B. ^[7] ; Cesarz, Carlos L. ^{[2, 8]} ; Carvalho, Hernandes F. ^{[2, 1]}

Affiliation

^[1] Univ Estadual Campinas, Dept Struct & Funct Biol, Rua Charles Darwin S-N, Bld N, Rooms 10-11, BR-13083863 Campinas, SP - Brazil

^[2] Natl Inst Sci & Technol Photon Appl Cell Biol INF, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

^[4] Jundiai Med Sch, Dept Pathol, Jundiai, SP - Brazil

^[5] Univ Estadual Campinas, Dept Genet Evolut Microbiol & Immunol, Campinas, SP - Brazil

^[6] Sao Paulo State Univ, Dept Morphol, Botucatu, SP - Brazil

^[7] Univ Fed Minas Gerais, Dept Morphol, Belo Horizonte, MG - Brazil

^[8] Univ Estadual Campinas, Dept Quantum Elect, Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 234, n. 10, p. 19048-19058, OCT 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression
• Grantee: Hernandes Faustino de Carvalho
• Support Opportunities: Research Projects - Thematic Grants