Transcriptome Analysis Reveals That NEFA and β-Hydroxybutyrate Induce Oxidative Stress and Inflammatory Response in Bovine Mammary Epithelial Cells.
Transcriptome Analysis Reveals That NEFA and β-Hydroxybutyrate Induce Oxidative Stress and Inflammatory Response in Bovine Mammary Epithelial Cells.
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DOI：
10.3390/metabo12111060
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发表时间：
2022-11-02
期刊：
影响因子：
4.1
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中科院分区：
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非酯化脂肪酸（NEFA）和β-羟基丁酸（BHBA）是奶牛围产期能量负平衡（NEB）启动的脂肪动员代谢产物，对牛多种细胞的生理功能有不良影响。本研究旨在探讨NEFA和BHBA在引发牛乳腺上皮细胞氧化应激和炎症反应中的生物学作用。RNA测序分析表明，NEFA、BHBA及其联合处理的BMEC分别有1343、48和1725个差异表达基因。GO功能分析显示DEG在“氧化应激反应”和“炎症反应”中显著富集。进一步的研究表明，NEFA和BHBA通过增加丙二醛（MDA）和活性氧（ROS）的积累，降低总超氧化物歧化酶（T-SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性，引起氧化应激。此外，在NEFA和BHBA刺激后，炎症标志物（NO、TNF-α、IL-6和IL-1β）的表达增加。从机制上讲，我们的数据表明，NEFA和BHBA激活MAPK信号通路。总之，我们的研究结果表明，NEFA和BHBA诱导氧化应激和炎症反应可能通过MAPK信号通路在BMEC。
Non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) are the metabolites of fat mobilization initiated by negative energy balance (NEB) during the perinatal period in dairy cows, which have an adverse effect on cell physiology of various bovine cell types. The aim of this study was to explore the biological roles of NEFA and BHBA on provoking oxidative stress and inflammatory responses in bovine mammary epithelial cells (BMECs). RNA sequencing analysis showed that there are 1343, 48, and 1725 significantly differentially expressed genes (DEGs) in BMECs treated with NEFA, BHBA and their combination. GO functional analysis revealed that the DEGs were significantly enriched in “response to oxidative stress” and “inflammatory response”. Further study demonstrated that NEFA and BHBA elevated the malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation and reduced the total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity to cause oxidative stress. In addition, expression of inflammatory markers (NO, TNF-α, IL-6, and IL-1β) were increased after NEFA and BHBA stimulation. Mechanistically, our data showed that NEFA and BHBA activated the MAPK signaling pathway. Collectively, our results indicate that NEFA and BHBA induce oxidative stress and inflammatory response probably via the MAPK signaling pathway in BMECs.
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