Selenoprotein

Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia (HSP), including SELENOI...

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to increase due in part to the obesity epidemic and to environmental exposures to metabolism disrupting chemicals. A single gavage exposure of male mice to Aroclor 1260 (Ar1260), an environmentally relevant mixture of non-dioxin-like polychlorinated biphenyls (PCBs), resulted in steatohepatitis and altered RNA modifications in selenocysteine tRNA 34 weeks post-exposure. Unbiased approaches identified the liver proteome, selenoproteins, and levels of 25 metals...

Selenium (Se) is a naturally occurring essential micronutrient that is required for human health. Selenium supports cellular antioxidant defense and possesses bioeffects such as anti-inflammation, anti-cancer, anti-diabetic, and cardiovascular and liver protective effects arising from Se-enhanced cellular antioxidant activity. Past studies on Se have focused on elucidating Se speciation in foods, biofortification strategies to produce Se-enriched foods to address Se deficiency in the population, and the biochemical activities of Se in health...

Transfer RNA (tRNA) modification is essential for proper protein translation, as these modifications play important roles in several biological functions and disease pathophysiologies. AlkB homolog 8 (ALKBH8) is one of the nine mammalian ALKBH family molecules known to regulate selenoprotein translation through the modification of the wobble uridine (U34) in tRNA; however, its specific biological roles remain unclear. In this study, we investigated the role of ALKBH8 using Alkbh8 -knockout ( Albkh8 -/- ) mice, which were observed to have reduced 5-methoxycarbonylmethyluridine (mcm5U) and (S)-5-methoxycarbonylhydroxymethyluridine levels; notably, the mcm5U level was partially compensated only in the brain...

Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model...

The interplay of genetic, immune and environmental factors strongly contributes to the development of autoimmune thyroid disease (AITD), which can be classified as Graves' disease (GD) or Hashimoto thyroiditis (HT). One of the most studied exogenous factors in the pathogenesis of AITD is selenium, which, in the form of selenoproteins, strengthens the antioxidative defence system of thyroid cells against superoxide production. Furthermore, it modulates inflammatory cytokine release and autoantibody production...

Selenophosphate synthetase (SEPHS) plays an essential role in selenium metabolism. Two mammalian SEPHS paralogues, SEPHS1 and SEPHS2, share high sequence identity and structural homology with SEPHS. Here, we report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p...

As one of the indispensable trace elements for both humans and animals, selenium widely participates in multiple physiological processes and facilitates strong anti-inflammatory, antioxidant, and immune enhancing abilities. The biological functions of selenium are primarily driven by its presence in selenoproteins as a form of selenocysteine. Broilers are highly sensitive to selenium intake. Recent reports have demonstrated that selenium deficiency can adversely affect the quality of skeletal muscles and the economic value of broilers; the regulatory roles of several key selenoproteins (e...

Ferroptosis is a form of programmed cell death involved in various types of acute kidney injury (AKI). It is characterized by inactivation of the selenoprotein, glutathione peroxidase 4 (GPX4), and upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Since urinary selenium binding protein 1 (SBP1/SELENBP1) is a potential biomarker for AKI, this study investigated whether SBP1 plays a role in AKI. First, we showed that SBP1 is expressed in proximal tubular cells in normal human kidney, but is significant downregulated in cases of AKI in association with reduced GPX4 expression and increased ACSL4 expression...

Countries face exasperating and inclement climate worldwide. Food and feed security could be their paramount life objective. The study aimed to investigate the impact of selenium on the protein content and distribution in different parts of rice. For this purpose, advanced selenium biofortified breeding material developed after generations of breeding efforts was investigated at the field area, rice research institute, Chengdu, China during cropping season 2021-22. The accumulation and distribution of selenium and protein contents were observed in various fractions of selenium-enriched rice (Z3057B) and positive control (727)...

Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression...

Selenoprotein N-related myopathy (SEPN1-RM) is a genetic disease that causes muscle weakness and respiratory failure. Germani et al.1 demonstrate that diaphragm weakness in SEPN1-RM is prevented by the inhibition of ER stress or ERO1 oxidoreductase regulated by transcription factor CHOP.

Bisphenol A (BPA) is a commonly used environmental toxicant, is easily exposed to the human body and causes testicular damage, sperm abnormalities, DNA damage and apoptosis, and interferes in the process spermatogenesis and steroidal hormone production along with obstruction in testes and epididymis development. Zinc (Zn), a potent regulator of antioxidant balance, is responsible for cellular homeostasis, enzymes and proteins activities during spermatogenesis for cell defence mechanisms in the testes. Selenium (Se) is required for spermatogenesis, antioxidant action and in the activities of different selenoproteins...

Leishmaniasis remains one of the main public health problems worldwide, with special incidence in the poorest populations. Selenium and its derivatives can be potent therapeutic options against protozoan parasites. In this work, 17 aryl selenoates were synthesized and screened against three species of Leishmania ( Leishmania major , Leishmania amazonensis , and Leishmania infantum ). Initial screening in promastigotes showed L. infantum species was more sensitive to selenoderivatives than the others. The lead Se-(2-selenocyanatoethyl) thiophene-2-carboselenoate ( 16 ) showed a half-maximal effective concentration of 3...

This study aims to explore the concentrations of Se and Hg in shellfish along the Gulf of Mannar (GoM) coast (Southeast India) and to estimate related risks and risk-based consumption limits for children, pregnant women, and adults. Se concentrations in shrimp, crab, and cephalopods ranged from 0.256 to 0.275 mg kg-1 , 0.182 to 0.553 mg kg-1 , and 0.176 to 0.255 mg kg-1 , respectively, whereas Hg concentrations differed from 0.009 to 0.014 mg kg-1 , 0.022 to 0.042 mg kg-1 and 0...

Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases...

Aquaculture has become one of the most attractive food production activities as it provides high-quality protein for the growing human population. However, the abiotic chronic stress of fish in intensive fish farming leads to a detrimental condition that affects their health and somatic growth, comprising productive performance. This work aims to comprehensively review the impact of alternative and novel dietary protein sources on fish somatic growth, metabolism, and antioxidative capacity under environmental/abiotic stressors...

SELENON -Related Myopathy ( SELENON -RM) is a rare congenital myopathy caused by mutations of the SELENON gene characterized by axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology commonly includes multiminicores or a dystrophic pattern but is often non-specific. The SELENON gene encodes selenoprotein N (SelN), a selenocysteine-containing redox enzyme located in the endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, the molecular mechanism(s) by which SelN deficiency causes SELENON -RM are undetermined...

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide. Numerous evidence has demonstrated that metabolic reprogramming serves as a hallmark associated with an elevated risk of NAFLD progression. Selenoprotein W (SelW) is an extensively expressed hepatic selenoprotein that plays a crucial role in antioxidant function. Here, we first demonstrated that SelW is a significantly distinct factor in the liver tissue of NAFLD patients through the Gene Expression Omnibus (GEO) database. Additionally, loss of SelW alleviated hepatic steatosis induced by a high-fat diet (HFD), and was accompanied by the regulation of metabolic and inflammatory pathways as verified by transcriptomic analysis...

Selenocysteine (Sec), the 21st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Sec is analogous to the common cysteine (Cys) amino acid but its selenium atom offers physical-chemical properties not provided by the corresponding sulfur atom in Cys. Catalytic sites with Sec in selenoproteins of vertebrates are under strong purifying selection but one enzyme, Glutathione Peroxidase 6 (GPX6), independently exchanged Sec for Cys less than one hundred million years ago in several mammalian lineages...