SIRT4 Expression Ameliorates the Detrimental Effect of Heat Stress via AMPK/mTOR Signaling Pathway in BMECs.
SIRT4 Expression Ameliorates the Detrimental Effect of Heat Stress via AMPK/mTOR Signaling Pathway in BMECs.
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SIRT4 表达通过 AMPK/mTOR 信号通路改善 BMEC 中热应激的有害影响
DOI：
10.3390/ijms232113307
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发表时间：
2022-11-01
影响因子：
5.6
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中科院分区：
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Sirtuin 4 （SIRT4）是SIRT家族的一员，据报道是参与线粒体抗氧化防御的关键因子。本研究旨在探讨SIRT4调控奶牛乳腺上皮细胞（BMECs）热应激诱导的氧化应激和乳蛋白合成的潜在分子机制。我们的研究结果表明，SIRT4在热应激乳腺组织中显著降低。bmes中SIRT4的缺失诱导ROS的产生，其表现为抗氧化酶活性的降低，通过介导线粒体分裂和融合相关的蛋白和mRNA水平改变线粒体形态。此外，我们发现SIRT4缺失或应激条件抑制乳蛋白以及脂质和葡萄糖合成相关基因的表达，并激活AMPK/mTOR信号通路。发现SIRT4表达增加具有相反的效果。然而，阻断AMPK/mTOR信号通路可抑制SIRT4对乳合成相关基因表达的调控功能。综上所述，我们的研究结果表明SIRT4可能通过调节奶牛AMPK/mTOR信号通路在维持乳腺功能中发挥关键作用，表明SIRT4可能是治疗奶牛热应激诱导的BMEC损伤和低产奶量的潜在分子靶点。
Sirtuin 4 (SIRT4), a member of the SIRT family, has been reported to be a key factor involved in antioxidant defense in mitochondria. This study aimed to explore the potential molecular mechanism via which SIRT4 regulates heat stress-induced oxidative stress and lactoprotein synthesis in bovine mammary epithelial cells (BMECs). Our results showed that SIRT4 was significantly decreased in heat stressed mammary tissue. Depletion of SIRT4 in BMECs induced the generation of ROS, which, as exhibited by the decreased activity of antioxidant enzymes, changed mitochondrial morphology through mediating protein and mRNA levels related to mitochondrial fission and fusion. Moreover, we found that depletion of SIRT4 or stress conditions inhibited the expression of milk proteins, as well as lipid and glucose synthesis-related genes, and activated the AMPK/mTOR signaling pathway. Increased SIRT4 expression was found to have the opposite effect. However, blocking the AMPK/mTOR signaling pathway could inhibit the regulatory function of SIRT4 in milk synthesis-related gene expression. In summary, our results suggest that SIRT4 may play critical roles in maintaining mammary gland function by regulating the AMPK/mTOR signaling pathway in dairy cows, indicating that SIRT4 may be a potential molecular target for curing heat stress-induced BMEC injury and low milk production in dairy cows.