Gene Set Enrichment Analysis of Selenium-Deficient and High-Selenium Rat Liver Transcript Expression and Comparison With Turkey Liver Expression

Abstract

Background Better biomarkers of selenium (Se) status and a better understanding of toxic Se biochemistry are needed to set safe dietary upper limits. In previous studies, differential expression (DE) of individual liver transcripts in rats and turkeys failed to identify a single transcript that was consistently and significantly (q < 0.05) altered by high Se. Objectives To evaluate the effect of Se status on rat liver transcript expression data at the level of gene sets, and to compare transcript expression in rats with that in turkeys to identify common regulated transcripts. Methods Gene set enrichment analysis (GSEA) was conducted on liver from weanling rats fed an Se-deficient basal diet (0.005 μg Se/g) supplemented with 0, 0.24 (Se-adequate), 2, or 5 μg Se/g diet as selenite for 28 d. In addition, transcript expression was compared with liver expression in turkeys fed 0, 0.4, 2, or 5 μg Se/g diet as selenite. Results Se deficiency significantly downregulated the rat selenoprotein gene set but also upregulated gene sets for a variety of pathways, processes, and disease states. GSEA of 2 compared with 0.24 μg Se/g found no significantly up- or downregulated gene sets, showing that 2 μg Se/g is not particularly toxic to the rat. GSEA analysis of 5 compared with 0.24 μg Se/g transcripts, however, found 27 significantly upregulated gene sets for a wide variety of conditions. Cross-species GSEA comparison of transcript expression, however, identified no common gene sets significantly and consistently regulated by high Se in rats and turkeys. In addition, comparison of individual marginally significant (unadjusted P < 0.05) DE transcripts between rats and turkeys also failed to find common transcripts. Conclusions The dramatic increase in significant liver transcript DE and GSEA gene sets in rats fed 5 compared with 2 μg Se/g clearly appears to be a biomarker for Se toxicity, albeit not Se-specific. These analyses, however, failed to identify specific transcripts or pathways, biological states, or processes that were directly linked with high Se status, strongly indicating that adaptation to high Se lies outside transcriptional regulation.

The health benefits of selenium in food animals: a review

“…Se exhibits antioxidant, anti-inflammatory, anticarcinogenic, potential antiviral and antibacterial activity [4]. Its biological function is achieved through the insertion of this trace element into a family of proteins known as selenoproteins [5]. Among these, glutathione peroxidase (GSH-Px) is a pivotal component of the antioxidant glutathione pathways which detoxifies lipid peroxides and provides protection of cellular and subcellular membranes against reactive oxygen species (ROS) damage [6].…”

Extracellular Vesicles Derived from Selenium-Deficient MAC-T Cells Aggravated Inflammation and Apoptosis by Triggering the Endoplasmic Reticulum (ER) Stress/PI3K-AKT-mTOR Pathway in Bovine Mammary Epithelial Cells

“…GO and KEGG analysis showed that differentially expressed mRNAs and lncRNA target genes were mainly involved in oxidative stress, oxidative phosphorylation, endocytosis, apoptosis, metabolism, and other processes. The transcriptional expression data of the liver in rats with an Se deficiency diet indicated that Se deficiency changed some biological states or processes, including oxidative phosphorylation, ROS, xenobiotic metabolism, fatty acid metabolism, and glutathione metabolism [46]. Other studies have shown that dietary Se consistently affects inflammatory or immune pathway signaling networks in liver and lung tissue in mice [47].…”

Keratinase improves the growth performance, meat quality and redox status of broiler chickens fed a diet containing feather meal

“…In this study, dietary supplementation of keratinase at both doses of 100,000 U/kg and 200,000 U/kg have a better redox status, indicated by higher GPX activity and lower MDA concentration, than those of the control. The better redox status in muscle by keratinase supplementation could be explained by 1) keratinase improved the digestibility of ash, which might improve the utilization of selenium; as a selenium-dependent enzyme ( Sunde, 2021 ), GPX activity could be improved by the selenium utilization ( Zhao et al, 2017 ); 2) keratinase can improve the hydrolysis of the proteins containing cysteine to release cysteine ( Gradisar et al, 2005 ; Huang et al, 2018 ), a precursor of glutathione, thus increase the body synthesis glutathione ( Dennis et al, 2019 ); 3) glutathione/GPX system plays an important role in protecting the cells against oxidative stress ( Fu et al, 2007 ; Surai, 2020 ). Taken together, these findings could help explain that dietary supplementation of keratinase improved the meat quality relative to the control.…”