Selenium alleviates ER calcium depletion-induced endoplasmic reticulum stress dependent apoptosis via PERK/ATF4/CHOP pathway in chicken myocardium after mercuric chloride exposure

Mercury (Hg) is a highly toxic heavy metal with definite cardiotoxic properties. Selenium (Se) is a heart-healthy trace element and has been demonstrated to attenuate heavy metal induced organ toxicity. This study was designed to explore the antagonistic effect of Se on the cardiotoxicity of mercuric chloride (HgCl 2 ) in chicken. Histopathological observations demonstrated that Se attenuated HgCl 2 -induced myocardial injury, which was further confirmed by the results of serum CK and LDH levels assay and myocardial tissues oxidative stress indexes assessment. The results showed that Se prevented HgCl 2 -induced cytoplasmic Ca 2+ overload and endoplasmic reticulum (ER) Ca 2+ depletion mediated by Ca 2+ -regulatory dysfunction of the ER. Importantly, ER Ca 2+ depletion led to unfolded protein response (UPR) and endoplasmic reticulum stress (ERS), resulting in apoptosis of cardiomyocytes via the PERK/ATF4/CHOP pathway. Subsequently, the heat shock proteins expression activated by HgCl 2 through these stress responses, which was reversed by Se. Moreover, Se supplementation partially eliminated the effects of HgCl 2 on the expression of several ER-settled selenoproteins, including selenoprotein K (SELENOK), SELENOM, SELENON and SELENOS. In conclusion, these results suggested that Se alleviated ER Ca 2+ depletion and oxidative stress induced ERS dependent apoptosis via PERK/ATF4/CHOP pathway in chicken myocardium after HgCl 2 exposure.