Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in western China, NingXia University, NingXia, Yinchuan 750021, PR China; School of Life Science, NingXia University, NingXia, Yinchuan 750021, PR China.
Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in western China, NingXia University, NingXia, Yinchuan 750021, PR China; School of Life Science, NingXia University, NingXia, Yinchuan 750021, PR China.
Infect Genet Evol. 2020 Nov;85:104552. doi: 10.1016/j.meegid.2020.104552. Epub 2020 Sep 11.
Mycobacterial infection can induce alveolar macrophage apoptosis, which plays a vital role in the pathogenesis of tuberculosis. Accumulating evidence has demonstrated that fatty acid oxidation is involved in apoptosis during various pathological processes, including bacterial infection. However, whether fatty acid oxidation regulates mycobacterial infection-induced macrophage apoptosis remains unclear. Hence, the present study aimed to investigate the role of fatty acid binding protein 4 (FABP4) which is a carrier protein for fatty acids, in regulating apoptosis in RAW264.7 cells infected with Bacillus Calmette-Guerin (BCG). In our study, the impact of BCG infection on apoptosis and fatty acid oxidation in RAW264.7 cells was examined. Notably, we found that FABP4 was overexpressed during this process. Furthermore, small interfering RNAs targeting FABP4 were used to investigate the role of FABP4 in regulating apoptosis and fatty acid oxidation in BCG-infected RAW264.7 cells. The results indicated that mycobacterial infection promoted apoptosis and enhanced fatty acid oxidation in RAW264.7 cells. Moreover, FABP4 knockdown exacerbated BCG-induced apoptosis and upregulated the expression of p-PERK, p-eIF2α and chop, which are endoplasmic reticulum (ER) stress markers. In addition, FABP4 knockdown promoted fatty acid oxidation and ROS production, which result in the activation of ER stress. Our data suggested that FABP4 knockdown exacerbated BCG-induced apoptosis in RAW264.7 cells via the ER stress pathway.
分枝杆菌感染可诱导肺泡巨噬细胞凋亡，这在结核病的发病机制中起着至关重要的作用。越来越多的证据表明，脂肪酸氧化参与了包括细菌感染在内的各种病理过程中的细胞凋亡。然而，脂肪酸氧化是否调节分枝杆菌感染诱导的巨噬细胞凋亡尚不清楚。因此，本研究旨在探讨脂肪酸结合蛋白 4（FABP4）在调节感染卡介苗（BCG）的 RAW264.7 细胞凋亡中的作用。在我们的研究中，检测了 BCG 感染对 RAW264.7 细胞凋亡和脂肪酸氧化的影响。值得注意的是，我们发现在此过程中 FABP4 过表达。此外，使用针对 FABP4 的小干扰 RNA 来研究 FABP4 在调节 BCG 感染的 RAW264.7 细胞凋亡和脂肪酸氧化中的作用。结果表明，分枝杆菌感染促进了 RAW264.7 细胞的凋亡和脂肪酸氧化。此外，FABP4 敲低加剧了 BCG 诱导的细胞凋亡，并上调了内质网（ER）应激标志物 p-PERK、p-eIF2α 和 chop 的表达。此外，FABP4 敲低促进了脂肪酸氧化和 ROS 产生，从而激活了 ER 应激。我们的数据表明，FABP4 敲低通过 ER 应激途径加剧了 RAW264.7 细胞中 BCG 诱导的细胞凋亡。
