Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1(142)-macrophages
ARTIGO
Inglês
Agradecimentos: We thank Dr. J. Xavier Neto for providing the DS-red mice and Dr.Mario J. Saad for the iNOS KO mice. This study was funded byFAPESP (grant 2009/016150-6) and CNPq. INFABiC is cofunded byFAPESP and CNPq
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...
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
FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP
2009/016150-6
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ
Fechado
Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1(142)-macrophages
Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1(142)-macrophages
Fontes
Journal of cellular physiology Vol. 234, n. 10 (Oct., 2019), p. 19048-19058 |