SIRT3 affects mitochondrial metabolic reprogramming via the AMPK-PGC-1α axis in the development of benign prostatic hyperplasia.
Prostate
; 81(15): 1135-1148, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34411320
ABSTRACT
BACKGROUND:
Sirtuin 3 (SIRT3) has been reported to share an association with mitochondrial metabolic reprogramming. However, the molecular mechanism underlying is not well understood, especially in benign prostatic hyperplasia (BPH). Therefore, the purpose of this study was to research whether SIRT3 can affect the progression of BPH via the regulation of mitochondrial metabolic reprogramming.METHODS:
Following the development of a rat model of BPH using testosterone propionate (TP), we extracted prostate tissues from sham-operated and BPH rats. Subsequently, bioinformatics prediction was used to screen the genes differentially expressed in BPH. To verify the role played by SIRT3 in BPH, we injected AAV9-SIRT3 into rats, followed by TP treatment. Prostate epithelial cells (PEC) were treated with TP to assess the mitochondrial morphology, mitochondrial membrane potential, and expression of enzymes related to the oxidative phosphorylation pathway after SIRT3 expression alteration. Finally, we examined the expression of AMPK-PGC-1α pathway in tissues and cells.RESULTS:
SIRT3 was reduced in the prostate tissues of BPH rats. After overexpression of SIRT3, mitochondrial morphology was more stable in prostate tissues of BPH rats and in TP-treated PEC, with significant increases in mitochondrial membrane potential and in the expression of oxidative phosphorylation-related enzymes in the cytoplasm. Moreover, SIRT3 significantly activated the AMPK-PGC-1α signaling pathway, which maintained the stability of mitochondrial membrane potential as well as mitochondrial structure, thus alleviating the symptoms of BPH.CONCLUSION:
SIRT3 maintained the stability of mitochondrial membrane potential as well as mitochondrial structure by activating the AMPK-PGC-1α pathway, thereby alleviating the symptoms of BPH.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Próstata
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Hiperplasia Prostática
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Propionato de Testosterona
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Proteínas Quinases Ativadas por AMP
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Sirtuína 3
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article