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

LI Sijie; SU Luna; YU Jinling; HUANG Hai; WU Ziqi; TANG Zhaoxin; LIAO Jianzhao

doi:10.13557/j.cnki.issn1002-2813.2025.14.009

Abstract：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-Cu Ⅰ group,High-Cu Ⅱ group,and High-Cu Ⅲ 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 Ⅱand 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.