Sirtuin 3 regulation: a target to alleviate β-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells

Journal of Animal Science and Biotechnology

Research

Shanjiang Zhao¹  Haobo Zhang¹  Jianfei Gong¹  Huan Wang¹  Huabin Zhu¹  Yi Wang¹  Nuo Heng¹  Haoyu Wang¹  Zhihui Hu¹ 

[1] State Key Laboratory of Animal Nutrition, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China;

关键词: BHBA;    Dairy cows;    Granulosa cells;    Ketosis;    Mitochondrial function;    Sirt3;   

DOI  :  10.1186/s40104-022-00825-w

 received in 2022-08-26, accepted in 2022-12-11,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDuring the transition period, the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk, high yielding cows would enter a negative energy balance (NEB) that causes an increase in ketone bodies (KBs) and decrease in reproduction efficiency. The excess concentrations of circulating KBs, represented by β-hydroxybutyric acid (BHBA), could lead to oxidative damage, which potentially cause injury to follicular granulosa cells (fGCs) and delayed follicular development. Sirtuin 3 (Sirt3) regulates mitochondria reactive oxygen species (mitoROS) homeostasis in a beneficial manner; however, the molecular mechanisms underlying its involvement in the BHBA-induced injury of fGCs is poorly understood. The aim of this study was to explore the protection effects and underlying mechanisms of Sirt3 against BHBA overload-induced damage of fGCs.ResultsOur findings demonstrated that 2.4 mmol/L of BHBA stress increased the levels of mitoROS in bovine fGCs. Further investigations identified the subsequent mitochondrial dysfunction, including an increased abnormal rate of mitochondrial architecture, mitochondrial permeability transition pore (MPTP) opening, reductions in mitochondrial membrane potential (MMP) and Ca2+ release; these dysfunctions then triggered the caspase cascade reaction of apoptosis in fGCs. Notably, the overexpression of Sirt3 prior to treatment enhanced mitochondrial autophagy by increasing the expression levels of Beclin-1, thus preventing BHBA-induced mitochondrial oxidative stress and mitochondrial dysfunction in fGCs. Furthermore, our data suggested that the AMPK-mTOR-Beclin-1 pathway may be involved in the protective mechanism of Sirt3 against cellular injury triggered by BHBA stimulation.ConclusionsThese findings indicate that Sirt3 protects fGCs from BHBA-triggered injury by enhancing autophagy, attenuating oxidative stress and mitochondrial damage. This study provides new strategies to mitigate the fGCs injury caused by excessive BHBA stress in dairy cows with ketosis.

【 授权许可】

CC BY   
© The Author(s) 2023

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