College of Animal Science and Technology, Yangtze University, Jingzhou 434025, Hubei, China.
College of Animal Science and Technology, Yangtze University, Jingzhou 434025, Hubei, China.
Toxicol In Vitro. 2024 Dec;101:105941. doi: 10.1016/j.tiv.2024.105941. Epub 2024 Sep 13.
Chloroquine (CQ) is widely used in the therapy against malarial, tumor and recently the COVID-19 pandemic, as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway. We previously reported that CQ (20 μM, 36 h) could reprogram transcriptome, and impair multiple signaling pathways vital to porcine immature Sertoli cells (iSCs). However, whether CQ treatment could affect the metabolomic compositions of porcine iSCs remains unclear. Here, we showed that CQ (20 μM, 36 h) treatment of porcine iSCs induced significant changes of 63 metabolites (11 up and 52 down) by the metabolomics method, which were involved in different metabolic pathways. Caffeic acid and esculetin, the top two up-regulated metabolites, were validated by ELISA. The combined analysis of metabolomics and transcriptome showed caffeic acid and esculetin to be highly correlated with multiple differentially expressed genes (DEGs), including Ndrg1, S100a8, Sqstm1, S100a12, S100a9, Ill1, Lif, Ntn4 and Peg10. Furthermore, esculetin treatment (53 nM, 36 h) significantly decreased the viability and proliferation, suppressed the mitochondrial function, whereas promoted the apoptosis of porcine iSCs, similar to those by CQ treatment (20 μM, 36 h). Collectively, our results showed that CQ treatment induces metabolic changes, and its effect on porcine iSCs could be partially mediated by esculetin.
氯喹（CQ）广泛用于抗疟疾、肿瘤和最近的 COVID-19 大流行的治疗中，作为溶酶体趋向性药物抑制自噬途径中的内溶酶体运输。我们之前报道过 CQ（20 μM，36 h）可以重编程转录组，并损害猪未成熟支持细胞（iSCs）的多个对其至关重要的信号通路。然而，CQ 处理是否会影响猪 iSCs 的代谢组学组成尚不清楚。在这里，我们通过代谢组学方法表明，CQ（20 μM，36 h）处理猪 iSCs 诱导了 63 种代谢物（上调 11 种，下调 52 种）的显著变化，这些代谢物涉及不同的代谢途径。通过 ELISA 验证了前两种上调的代谢物咖啡酸和秦皮素。代谢组学和转录组学的综合分析表明，咖啡酸和秦皮素与多个差异表达基因（DEGs）高度相关，包括 Ndrg1、S100a8、Sqstm1、S100a12、S100a9、Ill1、Lif、Ntn4 和 Peg10。此外，秦皮素处理（53 nM，36 h）显著降低了猪 iSCs 的活力和增殖，抑制了线粒体功能，而促进了其凋亡，与 CQ 处理（20 μM，36 h）的效果相似。总之，我们的研究结果表明 CQ 处理会引起代谢变化，其对猪 iSCs 的作用可能部分由秦皮素介导。
