Selenium prevent cadmium-induced hepatotoxicity through modulation of endoplasmic reticulum-resident selenoproteins and attenuation of endoplasmic reticulum stress

Cong, Zhen; Ge, Jing; Lv, Mei-Wei; Zhang, Qi; Talukder, Milton; Li, Jinlong

doi:10.1016/j.envpol.2019.113873

Cited by 78 publications

(36 citation statements)

References 57 publications

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“…Here, we found that Se could suppress Cd-induced cytotoxicity by reducing the entry of Cd via ZIP8 (Figure 4A-C). These results generally coincide with recent studies which reported that Se mitigated Cd-induced toxicity by regulating selenoprotein synthesis through promoting selenoprotein transcription [31,42].…”

Section: Discussionsupporting

confidence: 92%

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

Liang

Tan

et al. 2021

IJMS

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The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

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Section: Discussionsupporting

confidence: 92%

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

Liang

Tan

et al. 2021

IJMS

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“…Selenium is an essential element involved in the regulation of cellular antioxidant capacity (Amuru et al, 2019) and thyroid hormone metabolism (Sobolev et al, 2018). Moreover, it was reported that selenium supplementation prevented Cdinduced hepatotoxicity through alleviation of endoplasmic reticulum stress and modulation of endoplasmic reticulum -resident selenoproteins (Zhang et al, 2020). Also, it improved tumor Necrosis Factor-alpha (TNF-α), interleukin-1beta (IL-1β), and vascular endothelial growth factor (VEGF) gene expression in infertile women who were selected for in vitro fertilization (Heidar et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Disturbances in Thyroid Hormone Metabolism in Rats Exposed to γ- Radiation and Carbon Tetrachloride: The Role of N- acetyl cysteine and Sodium Selenite

Abdel-Aziz

2021

Egypt. J. Rad.Sci.

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“…MDA, as a product of lipid peroxidation, is acknowledged to be an index of cellular damage and excessive oxidative stress [ 45 ]. SOD converts superoxide (O 2 − ) into H 2 O 2 , which is dissociated into H 2 O by CAT [ 46 ]. SOD levels indirectly reflect the capacity of organisms to neutralize ROS, and MDA content reflects the severity of the body’s exposure to free radicals [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…) into H 2 O 2 , which is dissociated into H 2 O by CAT [46]. SOD levels indirectly reflect the capacity of organisms to neutralize ROS, and MDA content reflects the severity of the body's exposure to free radicals [47].…”

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confidence: 99%

The influence on oxidative stress markers, inflammatory factors and intestinal injury-related molecules in Wahui pigeon induced by lipopolysaccharide

Wang

Zhong

et al. 2021

PLoS ONE

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Introduction The intestinal structure is the foundation for various activities and functions in poultry. An important question concerns the changes in the intestinal status under endotoxin stimulation. This study aimed to investigate the mechanism of intestinal injury induced by lipopolysaccharide (LPS) in Wahui pigeons. Methods Thirty-six 28-day-old healthy Wahui pigeons were randomly divided into two groups. The experimental group was injected with LPS (100 μg/kg) once per day for five days, and the control group was treated with the same amount of sterile saline. Blood and the ileum were collected from pigeons on the first, third, and fifth days of the experiment and used for oxidative stress assessment, inflammatory factor detection, histopathological examination, and positive cell localization. In addition, intestinal injury indices and mRNA expression levels (tight junction proteins, inflammatory cytokines, and factors related to autophagy and apoptosis) were evaluated. Results Villi in the ileum were shorter in the LPS group than in the control group, and D-lactic acid levels in the serum were significantly increased. Glutathione and catalase levels significantly decreased, but the malondialdehyde content in the serum increased. TNF-α and IL-10 were detected at higher levels in the serum, with stronger positive signals and higher mRNA expression levels, in the LPS group than in the control group. In addition, the levels of TLR4, MyD88, NF-κB, and HMGB1 in the inflammatory signaling pathway were also upregulated. Finally, the mRNA expression of Claudin3, Occludin, and ZO-1 was significantly decreased; however, that of Beclin1 and Atg5 was increased in the LPS group. Conclusion Ileal pathological changes and oxidative stress were caused by LPS challenge; it is proposed that this triggering regulates the inflammatory response, causing excessive autophagy and apoptosis, promoting intestinal permeability, and leading to intestinal injury in Wahui pigeons.

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Selenium prevent cadmium-induced hepatotoxicity through modulation of endoplasmic reticulum-resident selenoproteins and attenuation of endoplasmic reticulum stress

Cited by 78 publications

References 57 publications

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

Disturbances in Thyroid Hormone Metabolism in Rats Exposed to γ- Radiation and Carbon Tetrachloride: The Role of N- acetyl cysteine and Sodium Selenite

The influence on oxidative stress markers, inflammatory factors and intestinal injury-related molecules in Wahui pigeon induced by lipopolysaccharide

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