Effect of high copper on mitochondrial unfolded protein response and expression of oxidative damage-related proteins in chicken hepatocytes

The study aimed to investigate the effects of high copper (Cu) on the mitochondrial unfolded protein response (UPRmt) and oxidative stress in chicken hepatocytes. A total of 240 one-day-old healthy white-feathered broilers were randomly divided into four groups, with six replicates per group and ten chickens per replicate. The control group was fed a basal diet (Cu: 11 mg/kg), while the High-CuⅠ group, High-CuⅡ group, and High-CuⅢ group were received diets containing 110, 220, and 330 mg/kg Cu, respectively. The test period was 42 days. The results showed that compared with the control group, obvious pathological damage occurred in the liver tissues of the High-Cu Ⅰ, Ⅱ, and Ⅲ groups, and there were obvious phenomena such as increased collagen fiber deposition and destruction of liver lobular structure in the High-Cu Ⅱ and Ⅲ groups. Compared with the control group, the relative mRNA expression level of deacetylase 3 (Sirt3) in the High-Cu Ⅱ group was significantly increased (P<0.05). The relative mRNA expression level of Sirt3 in the High-Cu Ⅲ group was extremely increased (P<0.01), and the mRNA expression level of heat shock protein 60 (HSP60) was significantly increased (P<0.05). The mRNA expression level of casein protease P (CLPP) in each experimental group was extremely increased (P<0.01). Compared with the control group, the relative expression levels of superoxide dismutase 2 (SOD2) and peroxide-reducing protein 3 (Prdx3) proteins in the High-Cu Ⅲ group were extremely increased (P<0.01). Compared with the control group, the relative expression level of CLPP protein in the High-Cu Ⅱ and Ⅲ groups was significantly increased (P<0.05), the relative expression level of HSP60 protein in the High-Cu Ⅱ group was extremely increased (P<0.01), and the relative expression level of heat shock protein family member A9 (HSPA9) protein in the High-Cu Ⅲ group was significantly increased (P<0.05). Compared with the control group, the number of Sirt3-positive particles in each experimental group increased significantly, and the brownish-yellow particles in the High-Cu Ⅲ group was more obvious. The positive expression level of HSP60 in the High-Cu Ⅰ group was extremely increased (P<0.01), and the positive expression level of HSP60 in the High-Cu Ⅱ group was significantly increased (P<0.05). The study indicates that high dietary Cu induces oxidative stress and UPRmt in chicken hepatocytes.