Expression Profile Analysis of Selenium-Related Genes in Peripheral Blood Mononuclear Cells of Patients with Keshan Disease

Abstract

Keshan disease (KD) is an endemic cardiomyopathy, which mainly occurs in China. Selenium deficiency is believed to play an important role in the pathogenesis of KD, but the molecular mechanism of selenium-induced damage remains unclear. To identify the key genes involved in selenium-induced damage, we compared the expression profiles of selenium-related genes between patients with KD and normal controls. Total RNA was isolated, amplified, labeled, and hybridized to Agilent human 4 × 44 K whole genome microarrays. Selenium-related genes were screened using the Comparative Toxicogenomics Database. The microarray data were subjected to single-gene and gene ontology (GO) expression analysis using R Studio and Gene Set Enrichment Analysis (GSEA) software. Quantitative real-time PCR was conducted to validate the microarray results. We identified 16 upregulated and 11 downregulated selenium-related genes in patients. These genes are involved in apoptosis, metabolism, transcription regulation, ion transport, and growth and development. Of the significantly enriched GO categories in KD patients, we identified four apoptosis-related, two metabolism-related, four growth and development-related, and four ion transport-related GOs. Based on our results, we suggest that selenium might contribute to the development of KD through dysfunction of selenium-related genes involved in apoptosis, metabolism, ion transport, and growth and development in the myocardium.

Therapeutic Benefits of Selenium in Hematological Malignancies

“…These studies have shown that, at supra-nutritional concentrations, MSC and SLM exhibit anti-angiogenic and anti-cancer effects. The well-studied inorganic selenium compound selenite ( Figure 2 ) is clinically utilized and supplemented in the diet of patients with the endemic Keshan disease [ 61 , 62 ]. Keshan disease arises due to insufficient dietary selenium levels, which can result in cardiovascular atrophy if not properly addressed [ 61 , 62 ].…”

“…The well-studied inorganic selenium compound selenite ( Figure 2 ) is clinically utilized and supplemented in the diet of patients with the endemic Keshan disease [ 61 , 62 ]. Keshan disease arises due to insufficient dietary selenium levels, which can result in cardiovascular atrophy if not properly addressed [ 61 , 62 ]. The supplementation of selenite into the diet successfully treats Keshan disease and the associated symptoms, suggesting the therapeutic benefits that can be imparted by selenite [ 61 , 62 ].…”

“…Keshan disease arises due to insufficient dietary selenium levels, which can result in cardiovascular atrophy if not properly addressed [ 61 , 62 ]. The supplementation of selenite into the diet successfully treats Keshan disease and the associated symptoms, suggesting the therapeutic benefits that can be imparted by selenite [ 61 , 62 ].…”

Synthesis and Types of Selenoproteins and Their Role in Regulating Inflammation and ER Stress Signaling Pathways: Overview

“…Both excess and deficiency of selenium cause some problems [2]. Selenium deficiency causes a number of problems such as acute heart failure, arrhythmia, muscular dystrophy, short stature, and short extremities [5][6][7]. On the other hand, excessive intake of Se causes hair loss, deterioration in nail structure, and nervous system anomalies [1,2].…”

Selenite Inhibits Notch Signaling in Cells and Mice

“…One form of inorganic selenium, anionic selenite (H 2 SeO 3 , dominantly HSeO 3 − in physiological pH), has been clinically adopted to treat Keshan disease. Keshan’s is an endemic disease caused by dietary selenium deficiency, ultimately leading to cardiovascular atrophy if left untreated [ 4 ]. Selenite supplemented via diet effectively rescues the symptoms observed in Keshan disease, indicating selenite’s potential to serve a wide range of biological functions.…”