SIRT3 protects bovine mammary epithelial cells from heat stress damage by activating the AMPK signaling pathway.
SIRT3 protects bovine mammary epithelial cells from heat stress damage by activating the AMPK signaling pathway.
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DOI：
10.1038/s41420-021-00695-7
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发表时间：
2021-10-21
影响因子：
7
通讯作者：
Chen KL
中科院分区：
文献类型：
--
作者：
Sun XC;Wang Y;Zeng HF;Xi YM;Lin H;Han ZY;Chen KL
随着全球气候变暖，热应激已成为全球乳制品行业面临的重要挑战。Sirtuin 3（SIRT3）是一种重要的线粒体NAD+依赖性脱羧酶，是细胞能量代谢和抗氧化防御的主要调节剂，是维持正常线粒体功能不可或缺的。本研究旨在探讨SIRT3对热应激诱导的牛乳腺上皮细胞（BMEC）损伤的保护作用及其机制。我们的研究结果表明，SIRT3在热应激乳腺组织和高温处理的BMEC中显著下调。SIRT3基因敲低可显著增加BMEC中HSP 70、Bax和切割型caspase 3的表达，抑制抗氧化酶的产生，从而促进ROS的产生和细胞凋亡。此外，SIRT3敲低可通过介导与线粒体分裂和融合相关的基因的表达来加重线粒体损伤，这些基因包括动力蛋白相关蛋白1、线粒体分裂1蛋白以及线粒体融合蛋白1和2。此外，SIRT3敲低显著降低BMEC中AMPK磷酸化。相反，高温处理中SIRT3过表达与SIRT3敲低在BMEC中具有相反的效果。SIRT3过表达可减轻热应激诱导的BMEC线粒体损伤，减弱氧化应激反应，促进AMPK磷酸化。综上所述，我们的结果表明SIRT3可以通过AMPK信号通路保护BMEC免受热应激损伤。因此，SIRT3降低氧化应激可能是夏季奶牛抵抗热应激的主要分子机制。
With global warming, heat stress has become an important challenge for the global dairy industry. Sirtuin 3 (SIRT3), an important mitochondrial NAD+dependent decarboxylase and a major regulator of cellular energy metabolism and antioxidant defense, is integral to maintaining normal mitochondrial function. The aim of this study was to assess the protective effect of SIRT3 on damage to bovine mammary epithelial cells (BMECs) induced by heat stress and to explore its potential mechanism. Our results indicate that SIRT3 is significantly downregulated in heat-stressed mammary tissue and high-temperature-treated BMECs. SIRT3 knockdown significantly increased the expression of HSP70, Bax, and cleaved-caspase 3 and inhibited the production of antioxidases, thus promoting ROS production and cell apoptosis in BMECs. In addition, SIRT3 knockdown can aggravate mitochondrial damage by mediating the expression of genes related to mitochondrial fission and fusion, including dynamin-related protein 1, mitochondrial fission 1 protein, and mitochondrial fusion proteins 1and 2. In addition, SIRT3 knockdown substantially decreased AMPK phosphorylation in BMECs. In contrast, SIRT3 overexpression in high-temperature treatment had the opposite effect to SIRT3 knockdown in BMECs. SIRT3 overexpression reduced mitochondrial damage and weakened the oxidative stress response of BMECs induced by heat stress and promoted the phosphorylation of AMPK. Taken together, our results indicate that SIRT3 can protect BMECs from heat stress damage through the AMPK signaling pathway. Therefore, the reduction of oxidative stress by SIRT3 may be the primary molecular mechanism underlying resistance to heat stress in summer cows.
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影响因子：
7
作者：
Akbarian A;Michiels J;Degroote J;Majdeddin M;Golian A;De Smet S
通讯作者：
De Smet S
影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
DOI：
10.3390/antiox7010013
发表时间：
2018-01-16
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Ježek J;Cooper KF;Strich R
通讯作者：
Strich R
影响因子：
1.9
作者：
Leroy, J. L. M. R.;Rizos, D.;Bols, P. E. J.
通讯作者：
Bols, P. E. J.
影响因子：
11.4
作者：
Cortese-Krott MM;Mergia E;Kramer CM;Lückstädt W;Yang J;Wolff G;Panknin C;Bracht T;Sitek B;Pernow J;Stasch JP;Feelisch M;Koesling D;Kelm M
通讯作者：
Kelm M