Copper serves as a co-factor for a host of metalloenzymes, particularly cytochrome c oxidase (COX). Although it is known that impaired COX function can lead to the excessive accumulation of reactive oxygen species (ROS), the mechanisms underlying how copper depletion leads to cell damage are poorly understood. Here, we have investigated the role of copper depletion during ferroptosis. The bathocuproinedisulfonic (BCS) treatment depolarized the mitochondrial membrane potential, increased the total cellular ROS levels, stimulated oxidative stress, and reduced the glutathione levels. Moreover, the depletion of copper limited the protein expression of glutathione peroxidase 4 (GPX4), which is the only enzyme that is known to prevent lipid peroxidation. Furthermore, we found that copper depletion decreased the sensitivity of the dermal papilla cells (DPCs) to erastin (an inducer of ferroptosis), and the ferroptosis inhibitor ferrostatin-1 (Fer-1) partially prevented BCS-mediated cell death. Overall, these findings establish a direct link between copper and ferroptosis; BCS-mediated copper depletion strongly enhances ferroptosis via mitochondrial perturbation and a reduction in antioxidative mechanisms.

Copper (Cu) is an important coenzyme factor in cell signaling, such as cytochrome c oxidase (Complex IV). Metabolism plays an important role in regulating the fate of mammalian cells. The aim of this study is to experimentally investigate the effect of copper on cell metabolism in the dermal papilla cells of the Rex rabbit. In this study, Cu promoted proliferation of dermal papilla cells (p = 0.0008) while also increasing levels of cellular CIII, CIV, Complex IV and ATP. Moreover, fifty metabolites that were significantly different between Cu and controls were identified as potential biomarkers of Cu stimulation. Copper-stimulated cells had altered levels of arachidonic acid derivatives, S-glutamic acid, and citric acid, which were primarily linked to two different pathways: arachidonic acid metabolism (p < 0.0001) and alanine, aspartate and glutamate metabolism (p = 0.0003). The addition of Cu can increase the proliferation of Rex rabbit dermal papilla cells. Increased levels of ubiquinol-cytochrome c reductase complex core protein 2 (CIII) and cytochrome c oxidase subunit 1 (CIV) were associated with the increased levels of cellular cytochrome c oxidase (Complex IV) and adenosine triphosphate (ATP). In a word, copper promotes cell proliferation by maintaining the function of the cellular mitochondrial electron transport chain (ETC) pathway.

BACKGROUND: As major stress hormones, glucocorticoids can directly or indirectly affect the intestinal microflora, although few studies have focused on changes in the composition of the intestinal microflora. In this study, rabbits were randomly divided into two groups: gavage administration with saline, and the same doses of dexamethasone (1 mg kg −1 ). After 7 days, the microbial diversity of the jejunum contents was analysed.RESULTS: The gut microflora richness and diversity had no significant difference between the two groups. The proportions of Firmicutes and Bacteroidetes were the most abundant in the jejunum of meat rabbits. Dexamethasone injection led to a change in the structure of the gut microflora composition, and we found that there were six biomarkers with linear discriminant analysis score >4 (Firmicutes, Caproiciproducens, Clostridiales, Clostridia, Psychrobacter, and Psychrobacter faecalis), moreover, the results of this study provide new insight into alleviating the effects of stress on meat rabbits. CONCLUSION: It was concluded that glucocorticoids caused changes in the composition of intestinal microflora.