Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1142 -macrophages.
J Cell Physiol
; 234(10): 19048-19058, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-30924162
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.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Próstata
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Apoptosis
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Estrés Oxidativo
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Células Epiteliales
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
J Cell Physiol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Brasil