Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto’s Thyroiditis

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto’s thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.

Assessment of Iodine and Selenium Nutritional Status in Women of Reproductive Age in Latvia

Background and Objectives: Adequate dietary intake of iodine and selenium is essential during pregnancy. While iodine is vital for maternal thyroid function and fetal development, selenium contributes to the regulation of thyroid function and thyroid autoimmunity. This study aimed to assess the consumption of iodine- and selenium-containing products by women of reproductive age and the iodine and selenium nutritional status of pregnant women in Latvia. Materials and Methods: Population health survey (2010–2018) data were used to characterize dietary habits in women of reproductive age. Additionally, 129 pregnant women in the first trimester were recruited; they completed a questionnaire and were tested for thyroid function, urinary iodine concentration (UIC), and serum selenium and selenoprotein P levels. Results: The use of some dietary sources of iodine (e.g., milk and dairy products) and selenium (e.g., bread) has decreased in recent years. Less than 10% of respondents reported the use of iodized salt. The use of supplements has become more common (reported by almost 50% of respondents in 2018). Dietary habits were similar in pregnant women, but the use of supplements was even higher (almost 70%). Nevertheless, most supplements used in pregnancy had insufficient contents of iodine and selenium. Thyroid function was euthyreotic in all women, but 13.9% of participants had a thyroid peroxidase antibodies (TPO-ab) level above 60 IU/mL. The median UIC (IQR) was 147.2 (90.0–248.1) μg/gCr, and 52.8% of pregnant women had a UIC below 150 μg/gCr. The mean selenium (SD) level was 101.5 (35.6) μg/L; 30.1% of women had a selenium level below 80 μg/L. The median selenoprotein P level was 6.9 (3.1–9.0) mg/L. Conclusions: Iodine nutrition in Latvian population of pregnant women was near the lower limit of adequate and a third of the population had a selenium deficiency. Supplements were frequently used, but most did not contain the recommended amounts of iodine and selenium.

Lack of Association between Common Polymorphisms in Selenoprotein P Gene and Susceptibility to Colorectal Cancer, Breast Cancer, and Prostate Cancer: A Meta-Analysis

Background and Objective. Selenoprotein P (SEPP1) is the major selenoprotein in plasma. Previous studies have demonstrated that SEPP1 expression was reduced in human prostate and colon tumors. Nowadays, studies concerning SEPP1 gene polymorphisms and cancer susceptibility have been extensively investigated, whereas results from these studies remain debatable rather than conclusive. Thus, we performed the present meta-analysis to comprehensively assess the association between two common polymorphisms (rs3877899 and rs7579) in SEPP1 and cancer susceptibility. Method. We search the PubMed, Embase, Google Scholar, and Wanfang (China) databases (up to December 1, 2020) to identify all eligible publications. The pooled odds ratio (OR) correspondence with 95% confidence interval (CI) was calculated to evaluate the associations. Results. Finally, nine eligible studies with 7,157 cases and 6,440 controls and five studies with 2,278 cases and 2,821 controls were enrolled in rs3877899 and rs7579 polymorphisms, individually. However, a null significant association was detected between the two polymorphisms in SEPP1 and susceptibility to colorectal, breast, and prostate cancer in all comparison models. Subsequently, subgroup analysis based on tumor type, no significant association was identified for prostate, breast, and colorectal cancer. In addition, when the stratification analyses were conducted by the source of control, HWE status, and ethnicity, yet no significant association was found. Conclusions. The current meta-analysis shows that SEPP1 rs3877899 and rs7579 polymorphisms may not be associated with susceptibility to colon cancer, breast cancer, and prostate cancer, and further well-designed studies with a larger sample size are warranted to validate our findings.

Effects of Bariatric Surgeries on Fetuin-A, Selenoprotein P, Angiopoietin-Like Protein 6, and Fibroblast Growth Factor 21 Concentration

Obesity is a civilization disease representing a global health problem. Excessive body weight significantly reduces the quality of life. It is also associated with the leading causes of death, including type 2 diabetes mellitus, cardiovascular diseases, and numerous types of cancer. The mainstay of therapy is a dietary treatment. However, in morbidly obese patients, dietary treatment is often insufficient. In these patients, the most effective procedure is bariatric surgery, but it is still difficult to predict its outcome and metabolic changes. Hepatokines are proteins secreted by hepatocytes. Many of them, including fetuin-A, selenoprotein P, angiopoietin-like protein 6, and fibroblast growth factor 21, have been linked to metabolic dysfunctions. In this context, hepatokines may prove helpful. This review investigates the possible changes in hepatokine profiles after selected bariatric surgery protocols. In this regard, Roux-en-Y gastric bypass is the most studied type of surgery. The overall analysis of published research identified fetuin-A as a potential marker of metabolic alternations in patients after bariatric surgery.

Selenoprotein P Regulates Synaptic Zinc and Reduces Tau Phosphorylation

Selenoprotein P (SELENOP1) is a selenium-rich antioxidant protein involved in extracellular transport of selenium (Se). SELENOP1 also has metal binding properties. The trace element Zinc (Zn2+) is a neuromodulator that can be released from synaptic terminals in the brain, primarily from a subset of glutamatergic terminals. Both Zn2+ and Se are necessary for normal brain function. Although these ions can bind together with high affinity, the biological significance of an interaction of SELENOP1 with Zn2+ has not been investigated. We examined changes in brain Zn2+ in SELENOP1 knockout (KO) animals. Timm-Danscher and N-(6-methoxy-8-quinolyl)-p-toluenesulphonamide (TSQ) staining revealed increased levels of intracellular Zn2+ in the SELENOP1−/− hippocampus compared to wildtype (WT) mice. Mass spectrometry analysis of frozen whole brain samples demonstrated that total Zn2+ was not increased in the SELENOP1−/− mice, suggesting only local changes in Zn2+ distribution. Unexpectedly, live Zn2+ imaging of hippocampal slices with a selective extracellular fluorescent Zn2+ indicator (FluoZin-3) showed that SELENOP1−/− mice have impaired Zn2+ release in response to KCl-induced neuron depolarization. The zinc/metal storage protein metallothionein 3 (MT-3) was increased in SELENOP1−/− hippocampus relative to wildtype, possibly in response to an elevated Zn2+ content. We found that depriving cultured cells of selenium resulted in increased intracellular Zn2+, as did inhibition of selenoprotein GPX4 but not GPX1, suggesting the increased Zn2+ in SELENOP1−/− mice is due to a downregulation of antioxidant selenoproteins and subsequent release of Zn2+ from intracellular stores. Surprisingly, we found increased tau phosphorylation in the hippocampus of SELENOP1−/− mice, possibly resulting from intracellular zinc changes. Our findings reveal important roles for SELENOP1 in the maintenance of synaptic Zn2+ physiology and preventing tau hyperphosphorylation.