Wang Mengran, Ma Feiyang, Zhong Gaolong, Liang Tingyu, Sun Bingxia, Liao Jianzhao, Hu Lianmei, Pan Jiaqiang, Tang Zhaoxin
College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China.
College of Animal Science, Anhui Science and Technology University, Chuzhou, Anhui 233100, China.
J Trace Elem Med Biol. 2024 Dec;86:127501. doi: 10.1016/j.jtemb.2024.127501. Epub 2024 Jul 23.
While copper (Cu) is essential for biological organisms, excessive Cu can be harmful. Ferroptosis is a programmed cell death pathway, but the role of ferroptosis in renal injury induced by Cu is limited. The aim of this study was to investigate the role of ferroptosis in kidney injury in chickens and the molecular mechanism by which Cu promotes renal ferroptosis.
Chicken were subjected to Cu treatment by artificially adding excess Cu to the basal diet (the Cu concentration in the diet was supplemented to 110-330 mg/kg), and the impact on kidney fibrosis, tissue structure, and ferroptosis-related molecular markers was studied. Then, the expression levels of genes and proteins related to ferroptosis, iron metabolism and ferroautophagy were detected to explore the promoting effect of Cu on ferroptosis in chicken kidney.
Cu treatment resulted in significant fibrosis and tissue structure damage in chicken kidneys. Molecular analysis revealed a significant upregulation of LC3Ⅱ, P62, ATG5, and NCOA4, along with a decrease in FTH1 and FTL protein levels. Additionally, crucial markers of ferroptosis, including the loss of GPX4, SLC7A11, and FSP1, and an increase in PTGS2 and ACSL4 protein levels, were observed in chicken kidneys after Cu exposure.
Our study showed that dietary Cu excess caused kidney injury in brochickens and exhibited ferroptosis-related features, including lipid peroxidation, reduction of ferritin, and downregulation of FSP1 and GPX4. These results indicate that excess Cu can induce renal ferroptosis and lead to kidney injury in chickens. This study highlights the complex interplay between Cu ions and ferroptosis in the context of renal injury and provides a new perspective for understanding the mechanism of Cu-induced renal injury.
虽然铜（Cu）对生物机体至关重要，但过量的铜可能有害。铁死亡是一种程序性细胞死亡途径，但铁死亡在铜诱导的肾损伤中的作用有限。本研究旨在探讨铁死亡在鸡肾损伤中的作用以及铜促进肾铁死亡的分子机制。
通过在基础日粮中人工添加过量铜（日粮中铜浓度补充至110 - 330mg/kg）对鸡进行铜处理，研究其对肾纤维化、组织结构和铁死亡相关分子标志物的影响。然后，检测与铁死亡、铁代谢和铁自噬相关的基因和蛋白质表达水平，以探讨铜对鸡肾铁死亡的促进作用。
铜处理导致鸡肾出现明显的纤维化和组织结构损伤。分子分析显示，LC3Ⅱ、P62、ATG5和NCOA4显著上调，同时FTH1和FTL蛋白水平降低。此外，在铜暴露后的鸡肾中观察到铁死亡的关键标志物，包括GPX4、SLC7A11和FSP1的缺失，以及PTGS2和ACSL4蛋白水平的增加。
我们的研究表明，日粮中铜过量会导致肉鸡肾损伤，并呈现出与铁死亡相关的特征，包括脂质过氧化、铁蛋白减少以及FSP1和GPX4下调。这些结果表明，过量的铜可诱导鸡肾铁死亡并导致肾损伤。本研究突出了在肾损伤背景下铜离子与铁死亡之间复杂的相互作用，并为理解铜诱导肾损伤的机制提供了新的视角。
