Selenium alleviates endoplasmic reticulum calcium depletion-induced endoplasmic reticulum stress and apoptosis in chicken myocardium after mercuric chloride exposure

Abstract

Mercury is a highly toxic heavy metal with definite cardiotoxic properties and can affect the health of humans and animals through diet. Selenium (Se) is a heart-healthy trace element and dietary Se has the potential to attenuate heavy metal-induced myocardial damage in humans and animals. This study was designed to explore antagonistic effect of Se on the cardiotoxicity of mercuric chloride (HgCl₂) in chickens. Hyline brown hens received a normal diet, a diet containing 250 mg/L HgCl₂, or a diet containing 250 mg/L HgCl₂ and 10 mg/kg Na₂SeO₃ for 7 weeks, respectively. Histopathological observations demonstrated that Se attenuated HgCl₂-induced myocardial injury, which was further confirmed by the results of serum creatine kinase and lactate dehydrogenase levels assay and myocardial tissues oxidative stress indexes assessment. The results showed that Se prevented HgCl₂-induced cytoplasmic calcium ion (Ca²⁺) overload and endoplasmic reticulum (ER) Ca²⁺ depletion mediated by Ca²⁺-regulatory dysfunction of ER. Importantly, ER Ca²⁺ depletion led to unfolded protein response and endoplasmic reticulum stress (ERS), resulting in apoptosis of cardiomyocytes via PERK/ATF4/CHOP pathway. In addition, heat shock protein expression was activated by HgCl₂ through these stress responses, which was reversed by Se. Moreover, Se supplementation partially eliminated the effects of HgCl₂ 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 Ca²⁺ depletion and oxidative stress-induced ERS-dependent apoptosis in chicken myocardium after HgCl₂ exposure.

Keywords: Apoptosis; Calcium ion homeostasis; Endoplasmic reticulum stress; Mercuric chloride; Myocardium; PERK/ATF4/CHOP pathway; Selenium.