Special Issue of “Optimal Selenium Status and Selenoproteins in Health”

Abstract

Selenium, an essential trace element, supports various cellular and physiological functions and prevents certain chronic and infectious diseases mainly through selenoproteins. At nutritional levels of intake, body selenium is mainly orchestrated for selenoprotein expression. Keshan disease is the first identified selenium-deficient syndrome characterized by congestive cardiomyopathy in the presence of a mutated strain of coxsackievirus B3 accompanied by severe selenium or glutathione peroxidase 1 deficiency [1]. It is becoming clear that selenium or selenoprotein deficiency implicates the pathogenesis of cancer, type 2 diabetes, neuronal degenerative diseases, and cardiovascular diseases in association with imbalance between generation and elimination of reactive oxygen or nitrogen species [2, 3]. Above nutritional needs (55 μg/day for adults), selenium may be beneficial at a very narrow window to prevent certain types of cancer [4]. As the doses increase, selenium toxicity may also exacerbate the disease, and therefore, its tolerable upper intake level is set at 400 μg/day in humans [5]. However, further research is needed to understand how this impacts selenoprotein pools in specific tissues/cells and non-specific incorporation of selenium and the mechanistic underpinnings in appropriate animal and cell models. There is a total of 25 selenoproteins in humans, and the numbers vary by species [2]. Human selenoproteins are categorized into glutathione peroxidases (GPX1-4; 6), thioredoxin reductases (TXNRD1-3), iodothyronine deiodinases (DIO1-3), the thioredoxin-like Rdx family (SELENOW, SELENOT, SELENOH, and SELENOV), and others (SELENOF, SELENOM, SELENOI, SELENOK, SELENOS, SELENOO, SELENON, SELENOP, methionine-R-sulfoxide reductase 1, and selenophosphate synthetase 2). While the list of human selenoproteins was confirmed in 2003 [6], many of them remain poorly studied and their functions less well understood. Another line of study that warrants further investigation is the biological role of non-selenoprotein and seleniummetabolites that are regulated by selenium deficiency and/or supranutritional levels of selenium [7]. This special issue encompasses two original research and six review articles. The two research articles investigate selenium interactions with other minerals. Guo et al. demonstrate a link between seleniumand magnesium-related genes through a cDNA microarray analysis of peripheral blood mononuclear cells from Keshan disease patients [8]. Furthermore, an international team from Russia, India, and China report the analysis of wheat samples grown in a seleniferous area of Punjab in India and show increases in a few other minerals in selenium-enriched wheat and bread [9]. While in vitro studies using such cereal extracts have led to alleviation of inflammatory gene expression in immune cells [10], the effect of consumption of selenium-enriched cereals on human and animal health remains to be further examined. Co-translational incorporation of selenocysteine is guided by in-frame UGA codons and the selenocysteine insertion sequence (SECIS) at the 3′-untranslated region of selenoprotein mRNAs, together with trans-acting factors [2]. Michael Howard and Paul Copeland discuss current understanding of UGA codon redefinition for selenoprotein expression and highlight two novel areas of selenocysteine incorporation research [11]. Lucia Seale, Marla Berry, and colleagues present an excellent review with a focus on selenoprotein degradation and selenocysteine recycling [12]. From a systems biology perspective, Yan Zhang and his colleague review selenium status and selenoproteins in human diseases [13]. The essentiality of selenium and selenoproteins in optimal health is specifically exemplified by in-depth reviews of SELENOP, GPX1, SELENOF, and selenium-binding protein 1 in prostate cancer * Wen-Hsing Cheng [email protected]