Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
Department of Biomedicine, University of Basel, Basel, Switzerland.
PLoS One. 2023 Oct 4;18(10):e0291950. doi: 10.1371/journal.pone.0291950. eCollection 2023.
System xc-, encoded by Slc7a11, is an antiporter responsible for exporting glutamate while importing cystine, which is essential for protein synthesis and the formation of thiol peptides, such as glutathione. Glutathione acts as a co-factor for enzymes responsible for scavenging reactive oxygen species. Upon exposure to bacterial products, macrophages exhibit a rapid upregulation of system xc-. This study investigates the impact of Slc7a11 deficiency on the functionality of peritoneal and bone marrow-derived macrophages. Our findings reveal that the absence of Slc7a11 results in significantly reduced glutathione levels, compromised mitochondrial flexibility, and hindered cytokine production in bone marrow-derived macrophages. Conversely, system xc- has a lesser impact on peritoneal macrophages in vivo. These results indicate that system xc- is essential for maintaining glutathione levels, mitochondrial functionality, and cytokine production, with a heightened importance under atmospheric oxygen tension.
系统 xc-，由 Slc7a11 编码，是一种反向转运体，负责输出谷氨酸的同时摄取半胱氨酸，这对半胱氨酸对于蛋白质合成和硫醇肽（如谷胱甘肽）的形成至关重要。谷胱甘肽作为负责清除活性氧物质的酶的辅助因子。巨噬细胞在接触细菌产物后会迅速上调系统 xc-。本研究探讨了 Slc7a11 缺乏对腹腔和骨髓来源巨噬细胞功能的影响。我们的研究结果表明，Slc7a11 的缺失会导致谷胱甘肽水平显著降低、线粒体的灵活性受损，以及骨髓来源巨噬细胞中细胞因子的产生受到抑制。相反，系统 xc-在体内对腹腔巨噬细胞的影响较小。这些结果表明，系统 xc-对于维持谷胱甘肽水平、线粒体功能和细胞因子的产生至关重要，在大气氧张力下更为重要。
