Selenoprotein-P1 (SEPP1) Expression in Human Proximal Tubule Cells after Ischemia-Reperfusion Injury: An In Vitro Model.

Background and Objectives: Selenium deficiency represents a risk factor for the occurrence of severe diseases, such as acute kidney injury (AKI). Recently, selenoprotein-p1 (SEPP1), a selenium transporter, mainly released by the liver, has emerged as a promising plasmatic biomarker of AKI as a consequence of cardio-surgery operations. The aim of the present study was to investigate, on an in vitro model of hypoxia induced in renal tubular cells, HK-2, the effects of sodium selenite (Na2SeO3) and to evaluate the expression of SEPP1 as a marker of injury. Materials and Methods: HK-2 cells were pre-incubated with 100 nM Na2SeO3 for 24 h, and then, treated for 24 h with CoCl2 (500 µM), a chemical hypoxia inducer. The results were derived from an ROS assay, MTT, and Western blot analysis. Results: The pre-treatment determined an increase in cells' viability and a reduction in reactive oxygen species (ROS), as shown by MTT and the ROS assay. Moreover, by Western blot an increase in SEPP1 expression was observed after hypoxic injury as after adding sodium selenite. Conclusions: Our preliminary results shed light on the possible role of selenium supplementation as a means to prevent oxidative damage and to increase SEPP1 after acute kidney injury. In our in vitro model, SEPP1 emerges as a promising biomarker of kidney injury, although further studies in vivo are necessary to validate our findings.

Selenoprotein P-1 (SEPP1) as an Early Biomarker of Acute Kidney Injury in Patients Undergoing Cardiopulmonary Bypass.

Background: Acute Kidney Injury (AKI) is a frequent, dangerous complication in patients undergoing cardiopulmonary bypass (CPB) with oxidative stress playing a crucial role. In this pilot study we evaluated the possible role of the selenoprotein-p1 (SEPP1), a circulating, anti-oxidant selenium transporter, as a predictive biomarker of AKI in this population setting. Methods: Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by Enzyme-Linked Immunosorbent Assay (ELISA). Results: SEPP1 increased from 69 [IQR 39-85] to 3263 [IQR 1886.2-5042.7] ng/mL (p for trend < 0.0001). AKI occurred in 26.7% of patients. In these individuals, an earlier and more prominent increase in SEPP1 was observed at 4 h and 8 h, as compared with those not experiencing AKI (difference between trends p < 0.0001). Logistic regression analyses evidenced 4 h and 8 h SEPP1 as significantly associated with AKI (OR 1.035; 95% CI 1.002-1.068; p = 0.03 and 1.011; 95% CI 1.002-1.021; p = 0.02, respectively). ROC analyses displayed a remarkable discriminatory capacity of early SEPP1 measurements in identifying AKI (AUCs ranging from 0.682 to 0.854; p from 0.04 to < 0.0001). In addition, 12 h-SEPP1 showed diagnostic capacity to identify patients reaching a secondary composite endpoint including major adverse kidney events (MAKEs). Conclusions: Findings from this pilot, exploratory study suggest that early SEPP1 measurement after CPB may hold great potential for improving renal risk stratification in cardiac surgery patients. Further studies in wider and more heterogeneous cohorts are needed to generalize these findings and to evaluate a possible applicability in daily practice.

No effect of modest selenium supplementation on insulin resistance in UK pregnant women, as assessed by plasma adiponectin concentration.

Concern has been expressed recently that Se may increase the risk of type 2 diabetes, but this has not been tested in a randomised-controlled trial (RCT) in pregnant women. We took advantage of having stored plasma samples from the Se in Pregnancy Intervention (SPRINT) RCT of Se supplementation in pregnancy to test the effect of Se supplementation on a marker of insulin resistance in UK pregnant women. Because our blood samples were not fasted, we measured plasma adiponectin concentration, a recognised marker of insulin resistance that gives valid measurements in non-fasted samples, as diurnal variability is minor and there is no noticeable effect of food intake. In SPRINT, 230 primiparous UK women were randomised to treatment with Se (60 µg/d) or placebo from 12 weeks of gestation until delivery. We hypothesised that supplementation with Se at a nutritional level would not exacerbate the fall in adiponectin concentration that occurs in normal pregnancy, indicating the lack of an adverse effect on insulin resistance. Indeed, there was no significant difference between the two groups in the change in adiponectin from 12 to 35 weeks (P=0·938), nor when the analysis was restricted to the bottom or top quartiles of baseline whole-blood Se (P=0·515 and 0·858, respectively). Cross-sectionally, adiponectin concentration was not associated with any parameter of Se status, either at 12 or 35 weeks. It is reassuring that a nutritional dose of Se had no adverse effect on the concentration of adiponectin, a biomarker of insulin resistance, in pregnant women of modest Se status.

Decreased plasma thiol antioxidant barrier and selenoproteins as potential biomarkers for ongoing methylmercury intoxication and an individual protective capacity.

Manifestation of methylmercury (MeHg) toxicity depends on individual susceptibility to MeHg, as well as MeHg burden level. Therefore, biomarkers that reflect the protective capacity against MeHg are needed. The critical role of oxidative stress in the pathogenesis of MeHg cytotoxicity has been demonstrated. Because MeHg has high affinity for selenohydryl groups, sulfhydryl groups, and selenides, and causes posttranscriptional defects in selenoenzymes, proteins with selenohydryl and sulfhydryl groups should play a critical role in mediating MeHg-induced oxidative stress. Here, plasma oxidative stress markers and selenoproteins were investigated in MeHg-intoxicated rats showing neuropathological changes after 4 weeks of MeHg exposure. The thiol antioxidant barrier (-SHp) level significantly decreased 2 weeks after MeHg exposure, which is an early stage at which no systemic oxidative stress, histopathological changes, or clinical signs were detected. Diacron reactive oxidant metabolite (d-ROM) levels significantly increased 3 weeks after MeHg exposure, indicating the occurrence of systemic oxidative stress. Rats treated with lead acetate or cadmium chloride showed no changes in levels of -SHp and d-ROM. Selenoprotein P1 abundance significantly decreased in MeHg-treated rats, whereas it significantly increased in rats treated with Pb or Cd. Plasma selenium-dependent glutathione peroxidase (GPx3) activity also significantly decreased after MeHg exposure, whereas plasma non-selenoenzyme glutathione reductase activity significantly increased in MeHg-treated rats. The results suggest that decreased capacity of -SHp and selenoproteins (GPx3 and selenoprotein P) can be useful biomarkers of ongoing MeHg cytotoxicity and the individual protective capacity against the MeHg body burden.

Can hepatokines be regarded as novel non-invasive serum biomarkers of intrahepatic lipid content in obese children?

PURPOSE: Hepatokines are proteins produced by the liver and involved in regulating glucose and lipid metabolism. However, their role as the biomarkers of intrahepatic lipid content is not clear. The aim of the study was to evaluate the serum concentration of selected hepatokines: fibroblast growth factor-21 (FGF-21), selenoprotein P (SELENOP) and sex hormone-binding globulin (SHBG) in obese children. PATIENTS AND METHODS: The cross-sectional study included 86 obese children with suspected liver disease. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in children with liver steatosis in ultrasound with elevated alanine aminotransferase (ALT) serum activity and excluded other liver diseases. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). RESULTS: The concentration of FGF-21 and SELENOP was significantly higher and SHBG significantly lower in children with NAFLD compared to controls. Only FGF-21 level was significantly higher in NAFLD children than in obese patients without NAFLD. The significant positive correlation of FGF-21 with ALT, gamma glutamyltransferase (GGT), triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR), the degree of liver steatosis in ultrasound and TILC in 1H-MRS were found. The ability of serum FGF-21 to diagnose severe liver steatosis was significant. CONCLUSIONS: FGF-21 can be considered as a suitable biomarker in predicting TILC and fatty liver in obese children.

Helicase lymphoid-specifics and selenoprotein P1 are potential candidate genes in the progression and prognosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (AD) remains one of the most common cancers. Early diagnosis of AD improves therapeutic strategy and lengthens survival time. The objective of this study is to identify hub genes influencing the process of lung AD. METHODS: The microarray profiles of GSE43458 were extracted from the Gene Expression Omnibus (GEO) database to screen potential targets during lung AD. Differentially expressed genes (DEGs) between AD patients and normal controls were detected. Then gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed. Moreover, the major modules of protein-protein interaction (PPI) network of those DEGs were performed using the MCODE plug of the Cytoscape. The hub genes were validated in the Oncomine and GEPIA datasets. Additionally, the prognostic values of hub genes were evaluated in Kaplan Meier plotter and GEPIA databases. RESULTS: Totally, 859 DEGs were identified, including 278 up-regulated and 581 down-regulated genes. Functional annotation suggested those DEGs were related to cell adhesion, migration and motility. Besides, helicase lymphoid-specifics (HELLs) and selenoprotein P1 (SEPP1) were regarded as hub genes in AD. Then, the upregulation of HELLs and downregulation of SEPP1 were validated in the Oncomine and GEPIA databases, respectively. Moreover, Kaplan-Meier and GEPIA databases also suggested both HELLs and SEPP1 could affect the prognosis of lung AD patients. CONCLUSIONS: Our study demonstrated HELLs and SEPP1 were hub genes contributing to the progress of lung AD. They could be potential target genes for the diagnosis and therapy of lung AD.