Mechanism study of SIRT3 alleviating oxidative-stress injury in renal tubular cells by promoting mitochondrial biogenesis via regulating mitochondrial redox balance
10.12464/j.issn.1674-7445.2025276
- VernacularTitle:SIRT3通过调节线粒体氧化还原平衡增加线粒体生物合成减轻肾小管细胞氧化应激损伤的机制研究
- Author:
Yaojun LIU
1
;
Jun ZHOU
2
;
Jing LIU
2
;
Yunfei SHAN
1
;
Huhai ZHANG
1
;
Pan XIE
1
;
Liying ZOU
1
;
Lingyu RAN
1
;
Huanping LONG
1
;
Lunli XIANG
1
;
Hong HUANG
2
;
Hongwen ZHAO
1
Author Information
1. Department of Nephrology, the First Affiliated Hospital of Army Medical University (Southwest Hospital), Chongqing 400038, China.
2. .
- Publication Type:OriginalArticle
- Keywords:
Ischemia-reperfusion injury;
Oxidative stress;
Sirtuin3;
Peroxisome proliferator-activated receptor γ coactivator-1α;
Nuclear respiratory factor 1;
Mitochondrial transcription factor A;
Superoxide dismutase 2;
Adenosine monophosphate activated protein kinase α1
- From:
Organ Transplantation
2026;17(1):86-94
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H2O2 and divided into four groups: control (NC), 50 μmol/L H2O2, 110 μmol/L H2O2 and 150 μmol/L H2O2. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H2O2, and siSIRT3+H2O2. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O2•−) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H2O2 decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O2•− did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O2•− level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H2O2 group exhibited decreased cellular ATP levels, elevated mitochondrial O2•− levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H2O2 group showed a decrease in cellular ATP levels, an increase in mitochondrial O2•− levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H2O2 group, the siSIRT3+H2O2 group showed a decrease in cellular ATP levels, an increase in mitochondrial O2•− levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.
