Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study

ABSTRACT Objective: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). Subjects and methods: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. Results: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 μg/L), GO: 53.6 (43.5-60.0 μg/L), HT: 51.9 (44.6-58.5 μg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 μg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 μg/mL) and in HT patients: 0.35 (0.2-1.17 μg/mL) compared to C group patients: 1.00 (0.564.21 μg/mL) as well as to GD patients: 1.19 (0.62-2.5 μg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. Conclusion: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK

BACKGROUND: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. METHODS: The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. RESULTS: Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1alpha, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. CONCLUSION: These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.

Hepatokines as a Link between Obesity and Cardiovascular Diseases

Non-alcoholic fatty liver disease, which is considered a hepatic manifestation of metabolic syndrome, independently increases the risks of developing cardiovascular disease (CVD) and type 2 diabetes mellitus. Recent emerging evidence suggests that a group of predominantly liver-derived proteins called hepatokines directly affect the progression of atherosclerosis by modulating endothelial dysfunction and infiltration of inflammatory cells into vessel walls. Here, we summarize the role of the representative hepatokines fibroblast growth factor 21, fetuin-A, and selenoprotein P in the progression of CVD.

Influence of low-selenium diet on expression of selenium-binding protein 1 and selenoprotein P in mouse liver, kidney and brain tissues / 中国地方病学杂志

Objective To explore the influence of low-selenium diet on expression of selenium-binding protein 1 (SBP1) and selenoprotein P (Sel P) in liver,kidney and brain tissues.Methods C57BL/6 mice were randomly divided into four groups according to body weight:control group,low-selenium treatment for 4-,12-and 24-week groups,10 mice in each group,half male and half female.The control group was fed with normal diet (selenium content was 0.300 mg/kg),distilled water,and sacrificed at the 12th week; low-selenium treatment groups were fed with low-selenium diet(selenium content was 0.015 mg/kg),then sacrificed at the 4th,12th and 24th weeks,respectively.Expressions of SBP1 and Sel P in mouse liver,kidney and brain tissues were determined by Western blotting.Results Expressions of SBP1 and Sel P in low-selenium feed mouse liver tissue at the 4th,12th and 24th weeks were,respectively,as follows 0.11 ± 0.01,0.36 ± 0.01,0.59 ± 0.02 and 0.41 ± 0.01,0.39 ± 0.02,0.25 ± 0.02;in kidney,respectively,as follows 0.60 ± 0.03,0.20 ± 0.02,0.03 ± 0.01 and 0.88 ± 0.01,0.73 ± 0.03,0.85 ± 0.02; in brain,respectively,as follows 0.54 ± 0.03,0.11 ± 0.01,0.01 ± 0.01 and 0.50 ± 0.02,0.49 ± 0.03,0.38 ± 0.02.Expression of Sel P in low-selenium feed mouse liver,kidney and brain tissues was significantly decreased as compared to that of control group(1.00 ± 0.00,1.00 ± 0.00,all P ＜ 0.05),but SBP1 content was reduced at first and then rebounded in kidney,and was in decreasing trend in liver and brain tissues.Conclusion Low-selenium diet has a certain effect on expression of SBP1 and Sel P in mouse liver,kidney and brain tissues.

Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease

BACKGROUND: Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). METHODS: We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). RESULTS: Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007). CONCLUSION: Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

Expression and Clinical Significance Of Selenoprotein-P In The Tissues of Colorectal Cancer / 医学研究杂志

Objective To discuss the effect of selenoprotein P (SeP) on occurring and developing of colorectal cancer and its clinical significance by detecting the expression of SeP in adjacent mucosa of colorectal cancer, and in the cancer, metastatic lymph node and metastasis hepatic tissues.Methods Tissue microarray was constructed, the expression of SeP in adjacent mucosa of colorectal cancer, and in the cancer, metastatic lymph node and metastasis hepatic tissues were detected by means of immunohistochemistry.Results The positive rate of SeP were 48.4%,69.5%,66.7% and 61.5% in adjacent mucosa, tumor cell, lymph node metastasis and hepatic metastasis. The expression of adjacent mucosa was significantly lower than that in other three sites(?2=16.53,P

Multiple variant mRNAs with different length tandem repeats of (CAYYCC)n produced from bovine selenoprotein P-like protein gene

In contrast to selenoprotein Ps (SeIPs) from other animal species, bovine selenoprotein P-like-protein (SeIPLP) was found to contain a tandem repeat of (CAYYCC)(11). During an investigation into whether SeIPLP was a bovine substitute for SeIP or uniquely bovine, its mRNA was found to consist of multiple variants with different length tandem repeat, namely p(0) with (CAYYCC)(11), p(-4) lacking (CAYYCC)(4), p(-8) lacking (CAYYCC)(8), and p(-9) lacking (CAYYCC)(9). Although they were encoded on a single gene locus, neither classicalGT-AG: nor minor classAT-AC: donator-acceptor sequences for alternative splicing were identified. A subsequent S1 protection assay using oligonucleotides, whose sequence may occur as variants, performed against bovine poly(A)(+)RNA identified a total of nine variants. Judging from the sequence of these variants and the branch point mapping, the consensus sequence for recognition of the donator was CACCCCCAC: and of the acceptor and the branch point A nucleotide,ACCCC: CAT orACCCC: CATCCCCAT. Furthermore, when the p(0) insert mRNA was expressed in COS-7 cells derived from an African green monkey kidney, cDNAs corresponding to p(-8) and p(-9) could be isolated. Therefore, the bovine SeIPLP mRNAs consisted of multiple variants probably due to a novel splicing mechanism which was not bovine-specific but common to other mammals.

Multiple Variant mRNAs with Different Length Tandem Repeats of (CAYYCC)n Produced from Bovine Selenoprotein P-like Protein Gene

In contrast to selenoprotein Ps (SelPs) from other animal species, bovine selenoprotein P-like-protein (SelPLP) was found to contain a tandem repeat of (CAYYCC)11. During an investigation into whether SelPLP was a bovine substitute for SelP or uniquely bovine, its mRNA was found to consist of multiple variants with different length tandem repeat, namely p(0) with (CAYYCC)11, p(-4) lacking (CAYYCC)4, p(-8) lacking (CAYYCC)8, and p(-9) lacking (CAYYCC)9. Although they were encoded on a single gene locus, neither classical GT-AG nor minor class AT-AC donator-acceptor sequences for alternative splicing were identified. A subsequent S1 protection assay using oligonucleotides, whose sequence may occur as variants, performed against bovine poly(A)+RNA identified a total of nine variants. Judging from the sequence of these variants and the branch point mapping, the consensus sequence for recognition of the donator was CACCCCCAC and of the acceptor and the branch point A nucleotide, ACCCCCAT or ACCCCCATCCCCAT. Furthermore, when the p(0) insert mRNA was expressed in COS-7 cells derived from an African green monkey kidney, cDNAs corresponding to p(-8) and p(-9) could be isolated. Therefore, the bovine SelPLP mRNAs consisted of multiple variants probably due to a novel splicing mechanism which was not bovine-specific but common to other mammals.