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

Autor: Barbosa GO; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Silva JAF; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Siqueira-Berti A; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Nishan U; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Rosa-Ribeiro R; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Oliveira SBP; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Baratti MO; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil.; National Institute for Science and Technology of Photonics Applied to Cell Biology (INFABiC), Campinas, Sao Paulo, Brazil., Ferrucci D; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Santana JCO; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Damas-Souza DM; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Bruni-Cardoso A; Department of Biochemistry, University of Sao Paulo, Sao Paulo, São Paulo, Brazil., Augusto TM; Department of Pathology, Jundiai Medical School, Jundiai, São Paulo, Brazil., Corrêa-da-Silva F; Department of Genetics, Evolution, Microbiology, and Immunology, State University of Campinas, Campinas, São Paulo, Brazil., Moraes-Vieira PM; Department of Genetics, Evolution, Microbiology, and Immunology, State University of Campinas, Campinas, São Paulo, Brazil., Stach-Machado DR; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil., Felisbino SL; National Institute for Science and Technology of Photonics Applied to Cell Biology (INFABiC), Campinas, Sao Paulo, Brazil.; Department of Morphology, São Paulo State University, Botucatu, São Paulo, Brazil., Menezes GB; Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Cesar CL; National Institute for Science and Technology of Photonics Applied to Cell Biology (INFABiC), Campinas, Sao Paulo, Brazil.; Department of Quantum Electronics, State University of Campinas, Campinas, São Paulo, Brazil., Carvalho HF; Department of Structural and Functional Biology, State University of Campinas, Campinas, Sao Paulo, Brazil.; National Institute for Science and Technology of Photonics Applied to Cell Biology (INFABiC), Campinas, Sao Paulo, Brazil.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2019 Aug; Vol. 234 (10), pp. 19048-19058. Date of Electronic Publication: 2019 Mar 28.
DOI: 10.1002/jcp.28544
Abstrakt: 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.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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