Interplay between autophagy and apoptosis in selenium deficient cardiomyocytes in chicken

Dietary selenium (Se) deficiency can cause heart dysfunction, however the exact mechanism remains unclear. To understand this mechanism, 180 day-old chicks, divided into two groups, C (control group) and L (low Se group), were fed with either a Se-sufficient (0.23 mg/kg) or Se-deficient (0.033 mg/kg) diets for 25 days, respectively. Heart tissues and blood samples were collected. In L group, the activities of serum creatine kinase (CK) and creatine kinase-myoglobin (CK-MB) increased and typical ultrastructural apoptotic features were observed. Se deficiency up-regulated the mRNA levels of Cysteinyl aspartate specific proteinase 3 (Caspase-3), Cysteinyl aspartate specific proteinase 8 (Caspase-8), Cysteinyl aspartate specific proteinase 9 (Caspase-9), B cell lymphoma/leukemia 2 (Bcl-2), Bcl-2 Associated X Protein (Bax), (P < 0.05), whereas, the mRNA levels of Microtubuleassociated protein light chains 3-1 (LC3-1), Autophagy associated gene 5 (ATG-5), Mammalian target of rapamycin (mTOR), Dynein and Becline-1 were down-regulated (P < 0.05). Noticeably, Microtubuleassociated protein light chains 3-2 (LC3-2) mRNA level increased (P < 0.05) by 20%. Western blot results showed that Se deficiency decreased the expression of Becline-1 and LC3-1 protein, however, the expression of Bax, Caspase-3 and Cysteinyl aspartate specific proteinase 12 (Caspase-12) increased at protein levels. The present study revealed that Se deficiency induced apoptosis while inhibited autophagy in chicken cardiomyocytes through Bax/Bcl-2 inhibition and caspases-mediated cleavage of Becline-1. Moreover, correlation analysis illustrates that apoptosis and autophagy might function contradictorily. Altogether we conclude that Se deficient chicken cardiomyocytes experienced apoptosis rather than autophagy which is considered to be more pro-survival. (C) 2017 Elsevier Inc. All rights reserved.