Roles Of Oxidative Stress And Endoplasmic Reticulum Stress In Selenium Deficiency-Induced Apoptosis In Chicken Liver

Liver is known as one of the target organs for selenium deficiency and it deficiency in diets leads to liver injury and oxidative stress. Oxidative stress and endoplasmic reticulum(ER) stress are involved in different types of stress-induced injuries. Accordingly, ER stress plays a key role in oxidative stress induced apoptosis. Hepatic apoptosis can cause liver injury and disease, and is considered to be mainly mediated by two signaling pathways: the death acceptor and the mitochondrial pathways of cell death.However, recent research has demonstrated that ERS also mediates cell apoptosis. But there is little understanding of how Se acts in apoptosis in liver of birds. The aim of the present study was to evaluate the roles of oxidative stress and ER stress in selenium deficiency-induced apoptosis in chicken liver.Hy-line variety white laying hens(1 day old, n=180) were randomly divided into two groups: the L group(fed with a Se-deficient(Se 0.033 mg/kg) diet) and the control group(fed with a normal(Se 0.2mg/kg) diet). Factor-associated oxidative stress, catalase(CAT) activity, H2O2 production and the inhibition of hydroxyl radicals(?OH) in the chicken liver were determined on days 15, 25, 35, 45, 55 and 65, respectively. In addition, ER stress-related genes(GRP78, GRP94, ATF4, ATF6, Caspase12)and apoptosis-related genes(Caspase3 and Bcl-2) were examined by fluorescence quantitative PCR, in addition, GRP78, GRP94, CHOP, Caspase3 and Bcl-2 were examined by western blot analysis.Pathological changes in liver tissue were observed by an optical microscope, apoptosis levels were also measured using ultrastructural observations and the Td T-mediated d UTP nick end labeling(TUNEL)assay. The results showed that:(1) CAT activity and ?OH inhibition were decreased and that H2O2 production was increased in the low-Se group, which demonstrated that oxidative stress occurred in the chicken liver.(2) The levels of the ER stress-related genes(GRP78, GRP94, ATF4, ATF6, Caspase12) m RNA were increased(p < 0.05) and the levels of GRP78, GRP94 and CHOP protein were also increased(p <0.05). In addition, ER lesions of the chicken liver were observed by histopathologic observations in the low-Se group, which demonstrated that ER stress occurred in the chicken liver.(3) The expression of Caspase3 m RNA and protein increased(p < 0.05) and the expression of Bcl-2 m RNA and protein decreased(p < 0.05) than in the control group. In addition, apoptosis was observed by histopathologic and ultrastructural observations in chicken liver in the low-Se group. The degree and the number of apoptotic cells rose in a time-dependent manner by TUNEL assay, which demonstrated that apoptosis occurred in the chicken liver.These results indicated that the oxidative-ER stress pathway participates in Se deficiency-induced apoptosis in the chicken liver.