Dihydromyricetin attenuates heat stress-induced apoptosis in dairy cow mammary epithelial cells through suppressing mitochondrial dysfunction
Dihydromyricetin attenuates heat stress-induced apoptosis in dairy cow mammary epithelial cells through suppressing mitochondrial dysfunction
复制标题
二氢杨梅素通过抑制线粒体功能障碍减轻热应激诱导的奶牛乳腺上皮细胞凋亡
DOI：
10.1016/j.ecoenv.2021.112078
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发表时间：
2021-03-03
影响因子：
6.8
通讯作者：
Chen, Kun-Lin
中科院分区：
文献类型：
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作者：
Wang, Hui-Li;Xing, Guang-Dong;Chen, Kun-Lin
众所周知，奶牛生产对高温、高湿、辐射热源等环境因素非常敏感。高温引起的热应激是引起氧化应激和细胞凋亡的主要环境因素，影响奶牛乳腺的发育。二氢杨梅素（DMY）是从蛇葡萄中提取的天然黄酮类化合物；已被证明具有抗炎、抗肿瘤、保肝等多种药理作用。本研究旨在评估DMY对热应激诱导的奶牛乳腺上皮细胞（DCMECs）凋亡的保护作用并探讨其潜在机制。结果表明，热应激会引发热休克反应，降低 DCMEC 细胞的活力；用 DMY (25 μM) 预处理 DCMEC 12 小时可显着减轻热应激对细胞的负面影响。 DMY 可以通过抑制热应激引起的线粒体膜去极化和线粒体功能障碍、Bax 和 Caspase 3 活性以及氧化酶的调节来提供细胞保护作用，从而防止 DCMEC 中 ROS 的产生和细胞凋亡。重要的是，DMY 治疗可以通过介导线粒体裂变和融合相关基因的表达来减弱热应激诱导的线粒体断裂，包括 Dynamin 相关蛋白 1 (Drp1)、线粒体裂变 1 蛋白 (Fis1) 和 Mitofusin1, 2 (Mfn1, 2)。最重要的是，我们的研究结果表明，DMY 可以通过防止氧化应激、线粒体裂变和融合的不平衡来保护 DCMEC 免受热应激引起的损伤，这提供了有用的证据，表明 DMY 可以成为一种有前途的治疗药物，用于保护热应激引起的乳腺损伤和乳腺炎。
It is well known that the dairy cow production is very sensitive to environmental factors, including high temperature, high humidity and radiant heat sources. High temperature-induced heat stress is the main environmental factor that causes oxidative stress and apoptosis, which affects the development of mammary glands in dairy cows. Dihydromyricetin (DMY) is a nature flavonoid compound extracted from Ampelopsis grossedentata; it has been shown to have various pharmacological functions, such as anti-inflammation, antitumor and liver protection. The present study aims to evaluate the protective effect of DMY on heat stress-induced dairy cow mammary epithelial cells (DCMECs) apoptosis and explore the potential mechanisms. The results show that heat stress triggers heat shock response and reduces cell viability in DCMECs; pretreatment of DCMECs with DMY (25 ?M) for 12 h significantly alleviates the negative effects of heat stress on cells. DMY can provide cytoprotective effects by suppressing heat stress-caused mitochondrial membrane depolarization and mitochondrial dysfunction, Bax and Caspase 3 activity, and modulation of oxidative enzymes, thereby preventing ROS production and apoptosis in DCMECs. Importantly, DMY treatment could attenuate heat stress-induced mitochondrial fragmentation through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (Mfn1, 2). Above all, our findings demonstrate that DMY could protect DCMECs against heat stress-induced injury through preventing oxidative stress, the imbalance of mitochondrial fission and fusion, which provides useful evidence that DMY can be a promising therapeutic drug for protecting heat stress-induced mammary glands injury and mastitis.