Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base, Ministry of Science and Technology, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China; College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base, Ministry of Science and Technology, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.
Toxicol Appl Pharmacol. 2021 Apr 1;416:115469. doi: 10.1016/j.taap.2021.115469. Epub 2021 Feb 25.
Heat stress-induced oxidative stress in bovine mammary epithelial cells (BMECs) threatens the normal growth and development of bovine mammary tissue, resulting in lower milk production of dairy cows. The aim of the present study is to investigate the protective effects of S-allyl cysteine (SAC), an organosulfur component extracted from aged garlic, on heat stress-induced oxidative stress and apoptosis in BMECs and to explore its underlying mechanisms. Our results showed that heat stress treatment considerably decreased cell viability, whereas SAC treatment dose-dependently restored cell viability of BMECs under heat-stress conditions. In addition, SAC protected BMECs from heat stress-induced oxidative damage by inhibiting the excessive accumulation of reactive oxygen species (ROS) and increasing the activity of antioxidant enzymes. It also inhibited heat stress-induced apoptosis by reducing the ratio of Bax/Bcl-2 and blocking proteolytic the cleavage of caspase-3 in BMECs. Interestingly, we found that the protective effect of SAC on heat stress-induced oxidative stress and apoptosis was dependent on the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. SAC promoted the Nrf2 nuclear translocation in heat stress-induced BMECs. The results were also validated by Nrf2 and Keap1 knockdown experiments further demonstrating that Nrf-2 was indeed involved in the protective effect of SAC on heat stress-induced oxidative damage and apoptosis. In summary, our results showed that SAC could protect BMECs from heat stress-induced injury by mediating the Nrf2/HO-1 signaling pathway, suggesting that SAC could be considered as a therapeutic drug for attenuating heat stress-induced mammary gland diseases.
热应激诱导的奶牛乳腺上皮细胞（BMECs）氧化应激会威胁奶牛乳腺组织的正常生长和发育，导致产奶量下降。本研究旨在探讨从陈蒜中提取的有机硫成分 S-烯丙基半胱氨酸（SAC）对 BMECs 热应激诱导的氧化应激和凋亡的保护作用，并探讨其潜在机制。我们的研究结果表明，热应激处理显著降低了细胞活力，而 SAC 处理则以剂量依赖的方式恢复了热应激条件下 BMECs 的细胞活力。此外，SAC 通过抑制活性氧（ROS）的过度积累和增加抗氧化酶的活性，保护 BMECs 免受热应激诱导的氧化损伤。它还通过降低 Bax/Bcl-2 比值和阻断 caspase-3 的蛋白水解切割来抑制热应激诱导的凋亡。有趣的是，我们发现 SAC 对热应激诱导的氧化应激和凋亡的保护作用依赖于核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶-1（HO-1）信号通路。SAC 促进了热应激诱导的 BMECs 中 Nrf2 的核转位。Nrf2 和 Keap1 敲低实验进一步验证了这一结果，进一步表明 Nrf-2 确实参与了 SAC 对热应激诱导的氧化损伤和凋亡的保护作用。综上所述，我们的研究结果表明，SAC 可以通过调节 Nrf2/HO-1 信号通路来保护 BMECs 免受热应激诱导的损伤，这提示 SAC 可以被考虑作为一种减轻热应激诱导的乳腺疾病的治疗药物。
