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SIRT3 affects mitochondrial metabolic reprogramming via the AMPK–PGC‐1α axis in the development of benign prostatic hyperplasia
Author(s) -
Li Yongzhi,
Wang Qian,
Li Jingyu,
Shi Benkang,
Liu Yili,
Wang Ping
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24208
Subject(s) - sirt3 , ampk , sirtuin , mitochondrion , endocrinology , inner mitochondrial membrane , microbiology and biotechnology , prostate , prostate cancer , medicine , biology , mitochondrial biogenesis , chemistry , cancer research , phosphorylation , cancer , biochemistry , acetylation , protein kinase a , gene
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.