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番茄红素通过 NFE2L2 信号通路缓解 HO 诱导的奶牛乳腺上皮细胞氧化应激、炎症和细胞凋亡。

Lycopene alleviates HO-induced oxidative stress, inflammation and apoptosis in bovine mammary epithelial cells via the NFE2L2 signaling pathway.

机构信息

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Xinyang Rd. 5, 163319 Daqing, China.

出版信息

Food Funct. 2019 Oct 16;10(10):6276-6285. doi: 10.1039/c9fo01922g.

DOI:10.1039/c9fo01922g
PMID:31576860
Abstract

During the transition into lactation, bovine mammary epithelial cells (bMECs) are likely subjected to altered redox balance due to the high metabolic rate associated with the onset of lactation. In non-ruminants, lycopene (LYC), a naturally occurring hydrocarbon carotenoid, has attracted considerable attention as a potential natural agent against oxidative stress. The aim of this study was to investigate whether LYC alleviates oxidative injury in bMECs induced by H2O2 and the underlying molecular mechanisms. The primary bMEC and bovine MEC line MAC-T cells were treated with H2O2 (500 μM) and/or LYC (0.5, 1 or 2 μM) for 24 h. The results showed that treatment with LYC decreased H2O2-induced accumulation of intracellular reactive oxygen species (ROS), inflammatory cytokine (TNF-α, IL-6, and IL-1β) expression and the apoptosis rate. These effects were associated with the activation of the NFE2L2-antioxidant response element (ARE) pathway coupled with inactivation of the nuclear factor-κB (NF-κB) inflammatory and caspase/Bcl2 apoptotic pathways. The bMECs were transfected with NFE2L2 siRNA for 48 h and/or treated with H2O2 (500 μM) and/or LYC (2 μM) for another 24 h. The fact that transfection with NFE2L2 siRNA abrogated the protection of LYC against H2O2-induced accumulation of intracellular ROS, inflammatory cytokine expression and apoptosis suggested that this antioxidant transcription factor is essential for the protective mechanism induced by LYC. These results suggest that LYC might be a potent antioxidant in vivo that could be administered to ruminant animals during stressful periods such as the transition into lactation.

摘要

在泌乳过渡期间,由于与泌乳开始相关的高代谢率,牛乳腺上皮细胞(bMEC)可能会经历氧化还原平衡的改变。在非反刍动物中,番茄红素(LYC),一种天然存在的类异戊二烯碳氢化合物类胡萝卜素,作为一种潜在的天然抗氧化应激剂引起了相当大的关注。本研究旨在探讨 LYC 是否可以减轻 H2O2 诱导的 bMEC 氧化损伤及其潜在的分子机制。原代 bMEC 和牛 MEC 系 MAC-T 细胞用 H2O2(500 μM)和/或 LYC(0.5、1 或 2 μM)处理 24 h。结果表明,LYC 处理可降低 H2O2 诱导的细胞内活性氧(ROS)、炎症细胞因子(TNF-α、IL-6 和 IL-1β)表达和细胞凋亡率的积累。这些作用与 NFE2L2-抗氧化反应元件(ARE)途径的激活有关,同时伴有核因子-κB(NF-κB)炎症和 caspase/Bcl2 凋亡途径的失活。bMEC 用 NFE2L2 siRNA 转染 48 h,并用 H2O2(500 μM)和/或 LYC(2 μM)处理 24 h。用 NFE2L2 siRNA 转染可消除 LYC 对 H2O2 诱导的细胞内 ROS 积累、炎症细胞因子表达和细胞凋亡的保护作用,表明这种抗氧化转录因子是 LYC 诱导的保护机制所必需的。这些结果表明,LYC 可能是一种有效的体内抗氧化剂,可在反刍动物应激期(如泌乳过渡期间)给予动物。

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