Non-Esterified Fatty Acid Induces ER Stress-Mediated Apoptosis via ROS/MAPK Signaling Pathway in Bovine Mammary Epithelial Cells.
Non-Esterified Fatty Acid Induces ER Stress-Mediated Apoptosis via ROS/MAPK Signaling Pathway in Bovine Mammary Epithelial Cells.
复制标题
DOI：
10.3390/metabo12090803
复制
发表时间：
2022-08-27
期刊：
影响因子：
4.1
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Yan Y;Huang J;Huan C;Li L;Li C
已知在奶牛过渡期期间由负能量平衡（NEB）诱导的非酯化脂肪酸（NEFA）浓度升高对多种牛细胞类型具有毒性。然而，NEFA在牛乳腺上皮细胞（BMEC）中的作用仍不清楚。本研究旨在探讨NEFA在内质网应激及BMEC凋亡中的作用及其分子机制。结果表明，NEFA通过上调GRP 78、HSP 70、XBP 1、ATF 6、phosphor-PERK和phosphor-IRE 1 α的表达，增强内质网应激，激活未折叠蛋白反应（UPR）信号通路。我们还发现NEFA剂量依赖性地诱导BMEC凋亡，如流式细胞术分析和凋亡基因表达增加所示。RNA-seq分析显示NEFA可能通过ATF 4-CHOP轴诱导BMEC凋亡。从机制上讲，我们的数据表明，NEFA增加活性氧（ROS）水平，导致MAPK信号通路的激活。此外，槲皮素，一种众所周知的抗氧化剂，被发现可以减轻NEFA处理的BMEC中ER应激介导的凋亡。总的来说，我们的研究结果表明，NEFA诱导内质网应激介导的细胞凋亡，可能通过ROS/MAPK信号通路，槲皮素已被证明可以减轻NEFA处理的BMEC内质网应激介导的细胞凋亡。
Elevated concentrations of non-esterified fatty acid (NEFA) induced by negative energy balance (NEB) during the transition period of dairy cows is known to be toxic for multiple bovine cell types. However, the effect of NEFA in bovine mammary epithelial cells (BMECs) remains unclear. The present study aimed to explore the role and molecular mechanism of NEFA in endoplasmic reticulum (ER) stress and the subsequent apoptosis in BMECs. The results showed that NEFA increased ER stress and activated the three unfolded protein response (UPR) signaling sub-pathways by upregulating the expression of GRP78, HSP70, XBP1, ATF6, phosphor-PERK, and phosphor-IRE1α. We also found that NEFA dose-dependently induced apoptosis in BMECs, as indicated by flow cytometry analysis and increased apoptotic gene expression. RNA-seq analysis revealed that NEFA induced apoptosis in BMECs, probably via the ATF4-CHOP axis. Mechanistically, our data showed that NEFA increased reactive oxygen species (ROS) levels, resulting in the activation of the MAPK signaling pathway. Moreover, quercetin, a well-known antioxidant, was found to alleviate ER stress-mediated apoptosis in NEFA-treated BMECs. Collectively, our results suggest that NEFA induces ER stress-mediated apoptosis, probably via the ROS/MAPK signaling pathway, as quercetin has been shown to alleviate ER stress-mediated apoptosis in NEFA-treated BMECs.
登录
查看更多内容
影响因子：
3.7
作者：
Badr CE;Hewett JW;Breakefield XO;Tannous BA
通讯作者：
Tannous BA
影响因子：
4.6
作者：
Loor, Juan J.;Everts, Robin E.;Lewin, Harris A.
通讯作者：
Lewin, Harris A.
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
3.5
作者：
Gessner, D. K.;Koch, C.;Eder, K.
通讯作者：
Eder, K.
影响因子：
8.9
作者：
Kang, Ruifen;Li, Ruonan;Li, Chunmei
通讯作者：
Li, Chunmei