Antagonistic effects of selenium on cadmium-induced apoptosis by restoring the mitochondrial dynamic equilibrium and energy metabolism in chicken spleens.

Zhe Xu,Shu Li,Xi Jin,Tingru Pan,Tianqi Liu,Na Wan

doi:10.18632/oncotarget.17539

Abstract

The aim of this study was to investigate the mechanism of cadmium-induced apoptosis in chicken spleens and the antagonistic effects of selenium. We duplicated the selenium-cadmium interaction model and examined the expression of apoptosis-, immune-, mitochondrial dynamics- and energy metabolism-related genes. The results demonstrated that after treatment with cadmium, the frequency of apoptosis was significantly increased, and the morphological characteristics of apoptosis were observed. The expression of pro-apoptotic genes was increased, and that of anti-apoptotic genes was decreased. The mRNA levels of tumor necrosis factor-α and interlenkin-1β were observably increased, but the interlenkin-2 and interferon-γ levels were markedly decreased. Furthermore, the mRNA and protein levels of dynamin-related protein 1 and mitochondrial fission factor were significantly enhanced, whereas mitofusin 1, mitofusin 2, and optic atrophy 1 were markedly decreased. The expression of hexokinase 1, hexokinase 2, aconitase 2, lactate dehydrogenase A, lactate dehydrogenase B, succinatedehydrogenase B, pyruvate kinase and phosphofructokinase were also reduced. Selenium supplements remarkably attenuated cadmium-induced effects (p < 0.05). Based on the above results, conclude that the cadmium treatment promoted a mitochondrial dynamic imbalance and reduced energy metabolism, leading to apoptosis and immune dysfunction in chicken spleens, and selenium had an antagonistic effect on Cd-induced apoptosis.

Highlights

Cadmium (Cd) is a widespread heavy metal pollutant, which can be discharged into the environment during industrial production, including the production of batteries, metal plating, pigments and plastics [1]
Based on the above results, conclude that the cadmium treatment promoted a mitochondrial dynamic imbalance and reduced energy metabolism, leading to apoptosis and immune dysfunction in chicken spleens, and selenium had an antagonistic effect on Cd-induced apoptosis
Apoptosis plays an important role in stabilizing the homeostatic system in organisms [34]

Summary

Introduction

Cadmium (Cd) is a widespread heavy metal pollutant, which can be discharged into the environment during industrial production, including the production of batteries, metal plating, pigments and plastics [1]. In rat proximal tubular cells, Cd induced apoptosis by the breakdown of mitochondrial ΔΨ and overproduction of reactive oxygen species (ROS) [8, 9]. The breakdown of mitochondrial ΔΨ and the increased mitochondrial membrane permeability resulted in the release of cytochrome c (Cyt-c) from the mitochondria into the cytosol [10]. In pancreatic β-cells, Cd increased the expression of p53, leading to the release of Cyt-c and apoptosis [12]. Recent studies have suggested that Cd induces mitochondrial www.impactjournals.com/oncotarget fragmentation by increasing dynamin-related protein 1 (Drp1) expression [14, 15]. Manganese (Mn) induced deregulation of expression levels of mitochondria-shaping proteins and exacerbated fragmentation [16]. Several reports revealed that heavy metal toxicity led to energy metabolism dysfunction, resulting in apoptosis. The reduced glucose metabolism and energy production impaired the normal structure and function of cardiomyocytes, leading to apoptosis [19]

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