Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
Biofactors. 2022 Jul;48(4):934-945. doi: 10.1002/biof.1837. Epub 2022 Mar 24.
The copper (Cu) transporter proteins play an important role in the maintenance of the Cu homeostasis in the body. Lysyl oxidase (LOX) proteins are involved in crosslinking of collagens and elastin molecules resulting in the establishment of extracellular matrix (ECM) and require Cu for their functional activity. Although there are few reports showing the protective effects of Cu chelators, the mechanism behind protection remains unknown. The present study investigated the role of Cu transporter proteins in renal fibrosis. We used tubular epithelial cells and three different animal models of renal injury to investigate the induction of Cu transporter proteins in renal injury with different etiology. We used disulfiram, clioquinol as two Cu chelators and ammonium tetrathiomolybdate as a standard Cu chelator. In addition, β-aminopropionitrile (BAPN) was used as a standard LOX inhibitor. We demonstrated that renal fibrosis is associated with the induction of Cu transporter proteins such as ATP7A and Copper Transporter 1 (CTR1) but the Cu overload did not induce renal fibrosis. In addition, the Cu chelators inhibited renal fibrosis by inhibiting the Cu transporter proteins.
铜 (Cu) 转运蛋白在维持体内 Cu 平衡中发挥重要作用。赖氨酰氧化酶 (LOX) 蛋白参与胶原蛋白和弹性蛋白分子的交联，从而建立细胞外基质 (ECM)，并需要 Cu 来发挥其功能活性。尽管有一些报道显示 Cu 螯合剂具有保护作用，但保护背后的机制仍不清楚。本研究探讨了 Cu 转运蛋白在肾脏纤维化中的作用。我们使用肾小管上皮细胞和三种不同的肾脏损伤动物模型，研究了不同病因引起的肾脏损伤中 Cu 转运蛋白的诱导。我们使用了二硫代二戊腈、氯喹酸作为两种 Cu 螯合剂，以及四硫钼酸铵作为标准 Cu 螯合剂。此外，β-氨基丙腈 (BAPN) 被用作标准 LOX 抑制剂。我们证明，肾脏纤维化与 Cu 转运蛋白（如 ATP7A 和铜转运蛋白 1 (CTR1)）的诱导有关，但 Cu 过载不会引起肾脏纤维化。此外，Cu 螯合剂通过抑制 Cu 转运蛋白抑制肾脏纤维化。
