Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

Abstract

Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms. Although several functions have been attributed to this class, the majority of the proteins are involved in oxidative stress defense. Here, we discuss the kinetoplastid selenocysteine pathway and how selenium supplementation is able to alter the infection course of trypanosomatids in detail. These organisms possess the canonical elements required for selenoprotein production such as phosphoseryl tRNA kinase (PSTK), selenocysteine synthase (SepSecS), selenophosphase synthase (SelD or SPS), and elongation factor EFSec (SelB), whereas other important factors presented in mammal cells, such as SECIS binding protein 2 (SBP) and SecP 43, are absent. The selenoproteome of trypanosomatids is small, as is the selenoproteome of others parasites, which is in contrast to the large number of selenoproteins found in bacteria, aquatic organisms and higher eukaryotes. Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage. New experiments are necessary to determine how selenium acts, but evidence suggests that immune response modulation and increased host defense against oxidative stress contribute to control of the parasite infection.

Novel Heteroaryl Selenocyanates and Diselenides as Potent Antileishmanial Agents

“…During the last years, various reports have shown recognition of an increase in plasma selenium levels as a new defensive strategy against Leishmania infection (14,15). The choice of the chemical form for the selenium derivatives can modulate the level of this element on the basis of several metabolic routes (16).…”

Leishmanicidal Activities of Novel Methylseleno-Imidocarbamates

“…In addition, there is growing evidence suggesting a connection between selenium (Se) and parasites, particularly trypanosomatids. In fact, some parasites express selenoproteins (3,4) and metabolize Se (5).…”

“…Se derivatives have been shown to reduce parasitemia (3,6). Furthermore, they also decrease clinical manifestations (7,8) and mortality in infected mice.…”

Insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in Leishmania donovani

“…Studies have shown that Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Latest studies have also shown that Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage (Da Silva et al, 2014). It is, thus, interesting to understand the sequence level information of the proteins involved in Seleno-cysteine biosynthesis in Leishmania donovani .…”