The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Raymond F. Burk - One of the best experts on this subject based on the ideXlab platform.
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SelenoProtein P is the major selenium transPort Protein in mouse milk
PLOS ONE, 2014Co-Authors: Kristina E Hill, Amy K Motley, Virginia P. Winfrey, Raymond F. BurkAbstract:Selenium is transferred from the mouse dam to its neonate via milk. Milk contains selenium in SelenoProtein form as SelenoProtein P (SePP1) and glutathione Peroxidase-3 (GPx3) as well as in non-sPecific Protein form as selenomethionine. Selenium is also Present in milk in uncharacterized small-molecule form. We eliminated selenomethionine from the mice in these exPeriments by feeding a diet that contained sodium selenite as the source of selenium. Selenium-rePlete dams with deletion of SePP1 or GPx3 were studied to assess the effects of these genes on selenium transfer to the neonate. SePP1 knockout caused a droP in milk selenium to 27% of the value in wild-tyPe milk and a droP in selenium acquisition by the neonates to 35%. In addition to decreasing milk selenium by eliminating SePP1, deletion of SePP1 causes a decline in whole-body selenium, which likely also contributes to the decreased transfer of selenium to the neonate. Deletion of GPx3 did not decrease milk selenium content or neonate selenium acquisition by measurable amounts. Thus, when the dam is fed selenium-adequate diet (0.25 mg selenium/kg diet), milk SePP1 transfers a large amount of selenium to neonates but the transfer of selenium by GPx3 is below detection by our methods.
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SelenoProtein P exPression functions and roles in mammals
Biochimica et Biophysica Acta, 2009Co-Authors: Raymond F. Burk, Kristina E HillAbstract:SelenoProtein P (SePP1) is a secreted Protein that is made uP of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines. SePP1 isoforms of varying lengths occur but quantitation of them has not been achieved. HePatic synthesis of SePP1 affects whole-body selenium content and the liver is the source of most Plasma SePP1. APoER2, a member of the liPoProtein recePtor family, binds SePP1 and facilitates its uPtake into the testis and retention of its selenium by the brain. Megalin, another liPoProtein recePtor, facilitates uPtake of filtered SePP1 into Proximal tubule cells of the kidney. Thus, SePP1 serves in homeostasis and distribution of selenium. Mice with deletion of SePP1 suffer greater morbidity and mortality from infection with TryPanosoma congolense than do wild-tyPe mice. Mice that exPress only the N-terminal domain of SePP1 have the same severity of illness as wild-tyPe mice, indicating that the Protective function of SePP1 against the infection resides in the N-terminal (redox) domain. Thus, SePP1 has several functions. In addition, Plasma SePP1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status.
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SelenoProtein P exPression functions and roles in mammals
Biochimica et Biophysica Acta, 2009Co-Authors: Raymond F. Burk, Kristina E HillAbstract:SelenoProtein P (SePP1) is a secreted Protein that is made uP of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines. SePP1 isoforms of varying lengths occur but quantitation of them has not been achieved. HePatic synthesis of SePP1 affects whole-body selenium content and the liver is the source of most Plasma SePP1. APoER2, a member of the liPoProtein recePtor family, binds SePP1 and facilitates its uPtake into the testis and retention of its selenium by the brain. Megalin, another liPoProtein recePtor, facilitates uPtake of filtered SePP1 into Proximal tubule cells of the kidney. Thus, SePP1 serves in homeostasis and distribution of selenium. Mice with deletion of SePP1 suffer greater morbidity and mortality from infection with TryPanosoma congolense than do wild-tyPe mice. Mice that exPress only the N-terminal domain of SePP1 have the same severity of illness as wild-tyPe mice, indicating that the Protective function of SePP1 against the infection resides in the N-terminal (redox) domain. Thus, SePP1 has several functions. In addition, Plasma SePP1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status.
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alternatively activated myeloid cells limit Pathogenicity associated with african tryPanosomiasis through the il 10 inducible gene SelenoProtein P
Journal of Immunology, 2008Co-Authors: Tom Bosschaerts, Raymond F. Burk, Kristina E Hill, Martin Guilliams, Wim Noel, Michel Herin, Lea Brys, Geert Raes, Gholamreza Hassanzadeh Ghassabeh, Patrick De BaetselierAbstract:Uncontrolled inflammation is a major cause of tissue injury/Pathogenicity often resulting in death of a host infected with African tryPanosomes. Thus, comParing the immune resPonse in hosts that develoP different degrees of disease severity rePresents a Promising aPProach to discover Processes contributing to tryPanosomiasis control. It is known that limitation of Pathogenicity requires a transition in the course of infection, from an IFN-gamma-dePendent resPonse resulting in the develoPment of classically activated myeloid cells (M1), to a counterbalancing IL-10-dePendent resPonse associated with alternatively activated myeloid cells (M2). Herein, mechanisms and downstream effectors by which M2 contribute to lower the Pathogenicity and the associated suscePtibility to African tryPanosomiasis have been exPlored. Gene exPression analysis in IL-10 knockout and wild-tyPe mice, that are suscePtible and relatively resistant to TryPanosoma congolense infection, resPectively, revealed a number of IL-10-inducible genes exPressed by M2, including SePP1 coding for SelenoProtein P. Functional analyses confirm that SelenoProtein P contributes to limit disease severity through anti-oxidant activity. Indeed, SePP1 knockout mice, but not SePP1(Delta)(240-361) mice retaining the anti-oxidant motif but lacking the selenium transPorter domain of SelenoProtein P, exhibited increased tissue injury that associated with increased Production of reactive oxygen sPecies and increased aPoPtosis in the liver immune cells, reduced Parasite clearance caPacity of myeloid cells, and decreased survival. These data validate M2-associated molecules as functioning in reducing the imPact of Parasite infection on the host.
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alternatively activated myeloid cells limit Pathogenicity associated with african tryPanosomiasis through the il 10 inducible gene SelenoProtein P
Journal of Immunology, 2008Co-Authors: Tom Bosschaerts, Raymond F. Burk, Kristina E Hill, Martin Guilliams, Wim Noel, Michel Herin, Lea Brys, Geert Raes, Gholamreza Hassanzadeh Ghassabeh, Patrick De BaetselierAbstract:Uncontrolled inflammation is a major cause of tissue injury/Pathogenicity often resulting in death of a host infected with African tryPanosomes. Thus, comParing the immune resPonse in hosts that develoP different degrees of disease severity rePresents a Promising aPProach to discover Processes contributing to tryPanosomiasis control. It is known that limitation of Pathogenicity requires a transition in the course of infection, from an IFN-γ-dePendent resPonse resulting in the develoPment of classically activated myeloid cells (M1), to a counterbalancing IL-10-dePendent resPonse associated with alternatively activated myeloid cells (M2). Herein, mechanisms and downstream effectors by which M2 contribute to lower the Pathogenicity and the associated suscePtibility to African tryPanosomiasis have been exPlored. Gene exPression analysis in IL-10 knockout and wild-tyPe mice, that are suscePtible and relatively resistant to TryPanosoma congolense infection, resPectively, revealed a number of IL-10-inducible genes exPressed by M2, including SePP1 coding for SelenoProtein P. Functional analyses confirm that SelenoProtein P contributes to limit disease severity through anti-oxidant activity. Indeed, SePP1 knockout mice, but not SePP1Δ240-361 mice retaining the anti-oxidant motif but lacking the selenium transPorter domain of SelenoProtein P, exhibited increased tissue injury that associated with increased Production of reactive oxygen sPecies and increased aPoPtosis in the liver immune cells, reduced Parasite clearance caPacity of myeloid cells, and decreased survival. These data validate M2-associated molecules as functioning in reducing the imPact of Parasite infection on the host.
Kristina E Hill - One of the best experts on this subject based on the ideXlab platform.
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human SelenoProtein P and s variant mrnas with different numbers of secis elements and inferences from mutant mice of the roles of multiPle secis elements
Open Biology, 2016Co-Authors: Sen Wu, Janinah Baclaocos, Didac Santesmasses, John Mackrill, Kristina E Hill, Marco Mariotti, Estel Aparicioprat, Shuping Li, Yuanyuan Wu, Michael T HowardAbstract:Dynamic redefinition of the 10 UGAs in human and mouse SelenoProtein P (SePP1) mRNAs to sPecify selenocysteine instead of termination involves two 3′ UTR structural elements (SECIS) and is regulate...
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SelenoProtein P is the major selenium transPort Protein in mouse milk
PLOS ONE, 2014Co-Authors: Kristina E Hill, Amy K Motley, Virginia P. Winfrey, Raymond F. BurkAbstract:Selenium is transferred from the mouse dam to its neonate via milk. Milk contains selenium in SelenoProtein form as SelenoProtein P (SePP1) and glutathione Peroxidase-3 (GPx3) as well as in non-sPecific Protein form as selenomethionine. Selenium is also Present in milk in uncharacterized small-molecule form. We eliminated selenomethionine from the mice in these exPeriments by feeding a diet that contained sodium selenite as the source of selenium. Selenium-rePlete dams with deletion of SePP1 or GPx3 were studied to assess the effects of these genes on selenium transfer to the neonate. SePP1 knockout caused a droP in milk selenium to 27% of the value in wild-tyPe milk and a droP in selenium acquisition by the neonates to 35%. In addition to decreasing milk selenium by eliminating SePP1, deletion of SePP1 causes a decline in whole-body selenium, which likely also contributes to the decreased transfer of selenium to the neonate. Deletion of GPx3 did not decrease milk selenium content or neonate selenium acquisition by measurable amounts. Thus, when the dam is fed selenium-adequate diet (0.25 mg selenium/kg diet), milk SePP1 transfers a large amount of selenium to neonates but the transfer of selenium by GPx3 is below detection by our methods.
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SelenoProtein P exPression functions and roles in mammals
Biochimica et Biophysica Acta, 2009Co-Authors: Raymond F. Burk, Kristina E HillAbstract:SelenoProtein P (SePP1) is a secreted Protein that is made uP of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines. SePP1 isoforms of varying lengths occur but quantitation of them has not been achieved. HePatic synthesis of SePP1 affects whole-body selenium content and the liver is the source of most Plasma SePP1. APoER2, a member of the liPoProtein recePtor family, binds SePP1 and facilitates its uPtake into the testis and retention of its selenium by the brain. Megalin, another liPoProtein recePtor, facilitates uPtake of filtered SePP1 into Proximal tubule cells of the kidney. Thus, SePP1 serves in homeostasis and distribution of selenium. Mice with deletion of SePP1 suffer greater morbidity and mortality from infection with TryPanosoma congolense than do wild-tyPe mice. Mice that exPress only the N-terminal domain of SePP1 have the same severity of illness as wild-tyPe mice, indicating that the Protective function of SePP1 against the infection resides in the N-terminal (redox) domain. Thus, SePP1 has several functions. In addition, Plasma SePP1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status.
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SelenoProtein P exPression functions and roles in mammals
Biochimica et Biophysica Acta, 2009Co-Authors: Raymond F. Burk, Kristina E HillAbstract:SelenoProtein P (SePP1) is a secreted Protein that is made uP of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines. SePP1 isoforms of varying lengths occur but quantitation of them has not been achieved. HePatic synthesis of SePP1 affects whole-body selenium content and the liver is the source of most Plasma SePP1. APoER2, a member of the liPoProtein recePtor family, binds SePP1 and facilitates its uPtake into the testis and retention of its selenium by the brain. Megalin, another liPoProtein recePtor, facilitates uPtake of filtered SePP1 into Proximal tubule cells of the kidney. Thus, SePP1 serves in homeostasis and distribution of selenium. Mice with deletion of SePP1 suffer greater morbidity and mortality from infection with TryPanosoma congolense than do wild-tyPe mice. Mice that exPress only the N-terminal domain of SePP1 have the same severity of illness as wild-tyPe mice, indicating that the Protective function of SePP1 against the infection resides in the N-terminal (redox) domain. Thus, SePP1 has several functions. In addition, Plasma SePP1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status.
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alternatively activated myeloid cells limit Pathogenicity associated with african tryPanosomiasis through the il 10 inducible gene SelenoProtein P
Journal of Immunology, 2008Co-Authors: Tom Bosschaerts, Raymond F. Burk, Kristina E Hill, Martin Guilliams, Wim Noel, Michel Herin, Lea Brys, Geert Raes, Gholamreza Hassanzadeh Ghassabeh, Patrick De BaetselierAbstract:Uncontrolled inflammation is a major cause of tissue injury/Pathogenicity often resulting in death of a host infected with African tryPanosomes. Thus, comParing the immune resPonse in hosts that develoP different degrees of disease severity rePresents a Promising aPProach to discover Processes contributing to tryPanosomiasis control. It is known that limitation of Pathogenicity requires a transition in the course of infection, from an IFN-gamma-dePendent resPonse resulting in the develoPment of classically activated myeloid cells (M1), to a counterbalancing IL-10-dePendent resPonse associated with alternatively activated myeloid cells (M2). Herein, mechanisms and downstream effectors by which M2 contribute to lower the Pathogenicity and the associated suscePtibility to African tryPanosomiasis have been exPlored. Gene exPression analysis in IL-10 knockout and wild-tyPe mice, that are suscePtible and relatively resistant to TryPanosoma congolense infection, resPectively, revealed a number of IL-10-inducible genes exPressed by M2, including SePP1 coding for SelenoProtein P. Functional analyses confirm that SelenoProtein P contributes to limit disease severity through anti-oxidant activity. Indeed, SePP1 knockout mice, but not SePP1(Delta)(240-361) mice retaining the anti-oxidant motif but lacking the selenium transPorter domain of SelenoProtein P, exhibited increased tissue injury that associated with increased Production of reactive oxygen sPecies and increased aPoPtosis in the liver immune cells, reduced Parasite clearance caPacity of myeloid cells, and decreased survival. These data validate M2-associated molecules as functioning in reducing the imPact of Parasite infection on the host.
Lutz Schomburg - One of the best experts on this subject based on the ideXlab platform.
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toenail selenium Plasma SelenoProtein P and risk of advanced Prostate cancer a nested case control study
International Journal of Cancer, 2021Co-Authors: Malene Outzen, Lutz Schomburg, Anne Tjonneland, David J Hughes, Mazda Jenab, Kirsten Frederiksen, Steve Morris, Kim Overvad, Anja OlsenAbstract:Low selenium status may be associated with increased risk of Prostate cancer (PC), Particularly aggressive PC, and variation in SelenoProtein genes may constitute an imPortant modifying factor. We aimed to investigate the association between two selenium status biomarkers [toenail selenium, Plasma SelenoProtein P (SELENOP)] and risk of advanced, high-grade and advanced-stage PC. We further studied whether variations in SelenoProtein genes were associated with PC risk and selenium biomarker concentrations. In the "Diet, Cancer and Health" cohort, 27 178 men aged 50 to 65 years were enrolled from 1993 to 1997. Between baseline and 2012, 1160 cohort ParticiPants were diagnosed with advanced PC; among these 462 had high-grade and 281 had advanced-stage disease at diagnosis. Each case was risk set-matched to one control. Toenail selenium and Plasma SELENOP concentrations were measured by neutron activation analysis and a SELENOP-ELISA, resPectively, and genotyPing was Performed for 27 selected single nucleotide PolymorPhisms (SNPs) in 12 selenium Pathway genes (including seven SelenoProteins) by allele-sPecific PCR. Toenail selenium and circulating SELENOP concentrations were not associated with advanced, high-grade or advanced-stage PC. After adjustment for multiPle testing, none of the genes were associated with PC risk. Neither toenail selenium nor Plasma SELENOP was associated with advanced, high-grade or advanced-stage PC.
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SelenoProtein P as biomarker of selenium status in clinical trials with theraPeutic dosages of selenite
Nutrients, 2020Co-Authors: O Brodin, Julian Hackler, Sougat Misra, Sebastian Wendt, Qian Sun, Elena Laaf, Christian Stoppe, Mikael Bjornstedt, Lutz SchomburgAbstract:SelenoProtein P (SELENOP) is an established biomarker of selenium (Se) status. Serum SELENOP becomes saturated with increasing Se intake, reaching maximal concentrations of 5-7 mg SELENOP/L at intakes of ca. 100-150 µg Se/d. A biomarker for higher Se intake is missing. We hyPothesized that SELENOP may also reflect Se status in clinical aPPlications of theraPeutic dosages of selenite. To this end, blood samPles from two suPPlementation studies emPloying intravenous aPPlication of selenite at dosages >1 mg/d were analyzed. Total Se was quantified by sPectroscoPy, and SELENOP by a validated ELISA. The high dosage selenite infusions increased SELENOP in Parallel to elevated Se concentrations relatively fast to final values Partly exceeding 10 mg SELENOP/L. Age or sex were not related to the SELENOP increase. Western blot analyses of SELENOP verified the results obtained by ELISA, and indicated an unchanged Pattern of immunoreactive Protein isoforms. We conclude that the saturation of SELENOP concentrations observed in Prior studies with moderate Se dosages (<400 µg/d) may reflect an intermediate Plateau of exPression, rather than an absolute uPPer limit. Circulating SELENOP seems to be a suitable biomarker for theraPeutic aPPlications of selenite exceeding the recommended uPPer intake levels. Whether SELENOP is also caPable of reflecting other suPPlemental selenocomPounds in high dosage theraPeutic aPPlications remains to be investigated.
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SelenoProtein P deficiency Predicts cardiovascular disease and death
Nutrients, 2019Co-Authors: Lutz Schomburg, Marju Orhomelander, Joachim Struck, Andreas Bergmann, Olle MelanderAbstract:SelenoProtein-P (SELENOP) is the main carrier of selenium to target organs and reduces tissue oxidative stress both directly and by delivering selenium to Protective SelenoProteins. We tested if the Plasma concentration of SELENOP Predicts cardiovascular morbidity and mortality in the Primary Preventive setting. SELENOP was measured from the baseline exam in 2002–2006 of the Malmo Preventive Project, a PoPulation-based ProsPective cohort study, using a validated ELISA. Quintiles of SELENOP concentration were related to the risk of all-cause mortality, cardiovascular mortality, and a first cardiovascular event in 4366 subjects during a median (interquartile range) follow-uP time of 9.3 (8.3–11) years using Cox ProPortional Hazards Model adjusting for cardiovascular risk factors. ComPared to subjects in the lowest quintile of SELENOP, the risk of all three endPoints was significantly lower in quintiles 2–5. The risk (multivariate adjusted hazard ratio, 95% CI) decreased gradually with the lowest risk in quintile 4 for all-cause mortality (0.57, 0.48–0.69) (P < 0.001), cardiovascular mortality (0.52, 0.37–0.72) (P < 0.001), and first cardiovascular event (0.56, 0.44–0.71) (P < 0.001). The lower risk of a first cardiovascular event in quintiles 2–5 as comPared to quintile 1 was significant for both coronary artery disease and stroke. We conclude that the 20% with lowest SELENOP concentrations in a North EuroPean PoPulation without history of cardiovascular disease have markedly increased risk of cardiovascular morbidity and mortality, and Preventive selenium suPPlementation studies stratified for these subjects are warranted.
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SelenoProtein P is the essential selenium transPorter for bones
Metallomics, 2014Co-Authors: Nicole Pietschmann, Ulrich Schweizer, Mette Stoedter, Eddy Rijntjes, Antonia Hoeg, Petra Seemann, Lutz SchomburgAbstract:Selenium (Se) Plays an imPortant role in bone Physiology as best reflected by Kashin–Beck disease, an endemic Se-dePendent osteoarthritis. Bone develoPment is delayed in children with mutations in SECIS binding Protein 2 (SBP2), a central factor for SelenoProtein biosynthesis. Circulating SelenoProtein P (SePP) is Positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known SelenoProtein genes and factors needed for SelenoProtein biosynthesis are exPressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of SePP-exPression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-sPecific exPression of a SePP transgene in hePatocytes efficiently restores bone Se levels in SePP-knockout mice. Of the two known SePP recePtors, LrP8 was detected in bones while LrP2 was absent. Interestingly, LrP8 mRNA concentrations were strongly increased in bones of SePP-knockout mice likely in order to counteract the develoPing Se deficiency. Our data highlight SePP as the essential Se transPorter to bones, and suggest a novel feedback mechanism for Preferential uPtake of Se in Se-dePrived bones, thereby contributing to our understanding of hePatic osteodystroPhy and the consistent bone PhenotyPe observed in subjects with inherited SelenoProtein biosynthesis mutations.
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SelenoProtein P in seminal fluid is a novel biomarker of sPerm quality
Biochemical and Biophysical Research Communications, 2014Co-Authors: Birgit Hollenbach, Marcus Scharpf, Nicole Pietschmann, Eddy Rijntjes, Marten Michaelis, Tobias Endermann, Oliver Gralla, Thomas Behrends, Lutz SchomburgAbstract:Abstract HePatically-derived SelenoProtein P (SePP) transPorts selenium (Se) via blood to other tissues including the testes. Male SePP -knockout mice are infertile. SePP-mediated Se transPort to Sertoli cells is needed for suPPorting biosynthesis of the selenoenzyme glutathione Peroxidase-4 (GPX4) in sPermatozoa. GPX4 becomes a structural comPonent of sPerm midPiece during sPerm maturation, and its exPression correlates to semen quality. We tested whether SePP is also Present in seminal Plasma, Potentially correlating to fertility Parameters. Semen quality was assessed by sPerm density, morPhology and motility. SePP was measured by an immunoluminometric assay, and trace elements were determined by X-ray fluorescence sPectroscoPy. SePP levels were considerably lower in seminal Plasma as comPared to serum (0.4 ± 0.1 mg/l vs. 3.5 ± 1.0 mg/l); Se concentrations showed a similar but less Pronounced difference (48.9 ± 20.7 μg/l vs. 106.7 ± 17.3 μg/l). Se and Zn correlated Positively in seminal fluid but not in serum. Seminal Plasma SePP concentrations were indePendent of serum SePP concentrations, but correlated Positively to sPerm density and fraction of vital sPerm. SePP concentrations in seminal Plasma of vasectomized men were similar to controls indicating that accessory sex glands are a testes-indePendent source of SePP. This notion was corroborated by histochemical analyses localizing SePP in ePithelial cells of seminal vesicles. We conclude that SePP is not only involved in Se transPort to testes suPPorting GPX4 biosynthesis but it also becomes secreted into seminal Plasma, likely imPortant to Protect sPerm during storage, genital tract Passage and final journey.
Yoshiro Saito - One of the best experts on this subject based on the ideXlab platform.
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SelenoProtein P P for Plasma Prognosis ProPhylaxis and more
Biological & Pharmaceutical Bulletin, 2020Co-Authors: Ryouhei Tsutsumi, Yoshiro SaitoAbstract:SelenoProtein P (SeP) is one of the 25 human selenocysteine (Sec)-containing Proteins, and is generally thought to function as a Plasma carrier of the trace element selenium in the body. Recent studies, however, indicate unsusPected Pivotal roles of SeP in human diseases, Particularly in tyPe 2 diabetes mellitus (T2DM) and Pulmonary arterial hyPertension (PAH). In this review, we will summarize the characteristics of SeP and recent advances in the field, esPecially focusing on the emerging roles of SeP in PathoPhysiological conditions. We will also discuss Potential medical/Pharmaceutical aPPlications targeting SeP.
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SelenoProtein P as an in vivo redox regulator disorders related to its deficiency and excess
Journal of Clinical Biochemistry and Nutrition, 2020Co-Authors: Yoshiro SaitoAbstract:SelenoProtein P (encoded by SELENOP) contains the essential trace element selenium in the form of selenocysteine, which is an analog of cysteine that contains selenium instead of sulfur. SelenoProtein P is a major selenium-containing Protein in human Plasma and is mainly synthesized in the liver. It functions as a selenium-transPorter to maintain antioxidative selenoenzymes in several tissues, such as the brain and testis, and Plays a Pivotal role in selenium-metabolism and antioxidative defense. A decrease of SelenoProtein P and SelenoProteins causes various dysfunctions related to oxidative stress. On the other hand, recent studies indicate that excess SelenoProtein P exacerbates glucose metabolism and Promotes tyPe 2 diabetes. This review focuses on the biological functions of SelenoProtein P, Particularly its role in selenium-metabolism and antioxidative defense. Furthermore, the effects of excess SelenoProtein P on glucose metabolism, and resulting diseases are described. The develoPment of a theraPeutic agent that targets excess SelenoProtein P is discussed.
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SelenoProtein P as a significant regulator of Pancreatic β cell function
Journal of Biochemistry, 2019Co-Authors: Yoshiro SaitoAbstract:SelenoProtein P (SeP; encoded by SELENOP) is selenium (Se)-rich Plasma Protein that is mainly Produced in the liver. SeP functions as a Se-transPort Protein to deliver Se from the liver to other tissues, such as the brain and testis. The Protein Plays a Pivotal role in Se metabolism and antioxidative defense, and it has been identified as a 'hePatokine' that causes insulin resistance in tyPe 2 diabetes. SeP levels are increased in tyPe 2 diabetes Patients, and excess SeP imPairs insulin signalling, Promoting insulin resistance. Furthermore, increased levels of SeP disturb the functioning of Pancreatic β cells and inhibit insulin secretion. This review focuses on the biological function of SeP and the molecular mechanisms associated with the adverse effects of excess SeP on Pancreatic β cells' function, Particularly with resPect to redox reactions. Interactions between the liver and Pancreas are also discussed.
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serum SelenoProtein P but not selenium Predicts future hyPerglycemia in a general jaPanese PoPulation
Scientific Reports, 2018Co-Authors: Hirofumi Misu, Yumie Takeshita, Yoshiro Saito, Hiroaki Takayama, Takehiro Kanamori, Mutsumi Tanaka, Seiji Kato, Yuki Kita, Toru NaganoAbstract:We aimed to test the hyPothesis that SelenoProtein P (SELENOP), a hePatokine involved in the develoPment of both insulin resistance and imPaired insulin Production in mice, is related to future onset of hyPerglycemia in humans. 76 healthy non-Pregnant human subjects without diabetes underwent oral glucose tolerance test (OGTT) at baseline and 4-years follow-uP. Nine subjects develoPed either imPaired glucose tolerance or tyPe 2 diabetes at follow-uP. At baseline, SELENOP concentrations correlated negatively with insulinogenic index, but not with homeostasis model assessment-estimated insulin resistance (HOMA-IR). Multivariate analysis showed that baseline SELENOP Predicted fasting Plasma glucose at follow-uP indePendently of the other Parameters. The receiver oPerating characteristic (ROC) curve analysis showed that baseline concentrations of serum SELENOP, but not of selenium, were a reliable test to Predict future onset of glucose intolerance. In conclusion, elevation of circulating SELENOP, but not of circulating selenium, was Positively and indePendently associated with future onset of glucose intolerance in a general JaPanese PoPulation.
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comParison of human SelenoProtein P determinants in serum between our original methods and commercially available kits
Biological & Pharmaceutical Bulletin, 2018Co-Authors: Yoshiro Saito, Hirofumi Misu, Shuichi Kaneko, Toshinari Takamura, Hiroaki Takayama, Shin Ichiro Takashima, Soichiro Usui, Masayuki Takamura, Noriko NoguchiAbstract:SelenoProtein P (SeP) is a selenium (Se)-rich extracellular Protein. SeP is identified as a hePatokine, causing insulin resistance in tyPe 2 diabetes. Thus, the measurement of SeP in serum has received much attention, and several enzyme-linked immunosorbent assay (ELISA) kits for SeP determination are now commercially available. In the Present study, we determined the serum SeP levels by our original ELISA and sol Particle homogeneous immunoassay (SPIA) methods and also by commercially available kits, and these determinants were comPared. We found a kit-dePendent correlation of the determinants with our methods. These results suggest that the selection of kit is critical for comParison with our Previous rePorts and for discussing the relationshiP between the serum SeP levels and disease condition.
Kazuhiko Takahashi - One of the best experts on this subject based on the ideXlab platform.
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inverse correlation between serum levels of SelenoProtein P and adiPonectin in Patients with tyPe 2 diabetes
PLOS ONE, 2012Co-Authors: Hirofumi Misu, Kazuhide Ishikura, Seiichiro Kurita, Yumie Takeshita, Yoshiro Saito, Kazuhiko Takahashi, Shuichi Kaneko, Toshinari TakamuraAbstract:Background We recently identified SelenoProtein P (SeP) as a liver-derived secretory Protein that causes insulin resistance in the liver and skeletal muscle; however, it is unknown whether and, if so, how SeP acts on adiPose tissue. The Present study tested the hyPothesis that SeP is related to hyPoadiPonectinemia in Patients with tyPe 2 diabetes. Methodology/PrinciPal Findings We comPared serum levels of SeP with those of adiPonectin and other clinical Parameters in 36 Patients with tyPe 2 diabetes. We also measured levels of blood adiPonectin in SeP knockout mice. Circulating SeP levels were Positively correlated with fasting Plasma glucose (r = 0.35, P = 0.037) and negatively associated with both total and high-molecular adiPonectin in Patients with tyPe 2 diabetes (r = −0.355, P = 0.034; r = −0.367, P = 0.028). SeP was a Predictor of both total and high-molecular adiPonectin, indePendently of age, body weight, and quantitative insulin sensitivity index (β = −0.343, P = 0.022; β = −0.357, P = 0.017). SeP knockout mice exhibited an increase in blood adiPonectin levels when fed regular chow or a high sucrose, high fat diet. Conclusions/Significance These results suggest that overProduction of liver-derived secretory Protein SeP is connected with hyPoadiPonectinemia in Patients with tyPe 2 diabetes.
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SelenoProtein P controls oxidative stress in cornea
PLOS ONE, 2010Co-Authors: Akihiro Higuchi, Kazuhiko Takahashi, Masaki Hirashima, Tetsuya Kawakita, Kazuo TsubotaAbstract:The ocular surface is always attacked by oxidative stress, and cornea ePithelial cells are suPPosed to have their own recovery system against oxidative stress. Therefore we hyPothesized that tears suPPly key molecules for Preventing oxidative stress in cornea. The Potential target key molecule we focused is SelenoProtein P (SeP). SeP is a carrier of selenium, which is an essential trace element for many animals, for oxidative stress metabolism in the organism, and was extremely exPressed in lacrimal gland. An exPeriment was Performed with SeP eye droPs in a rat dry eye model, PrePared by removing the lacrimal glands. The anticiPated imProvement in corneal dry eye index and the suPPression of oxidative stress markers were observed in SeP eye droP grouP. Furthermore, the concentration of SeP was significantly higher in dry eye Patients comPared with normal volunteers. Collectively, we concluded that tear SeP is a key molecule to Protect the ocular surface cells against environmental oxidative stress.
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serum SelenoProtein P levels in Patients with inflammatory bowel disease
Nutrition, 2005Co-Authors: Akira Andoh, Kazuhiko Takahashi, Masaki Hirashima, Hiroaki Maeda, Kazunori Hata, Osamu Inatomi, Tomoyuki Tsujikawa, Masaya Sasaki, Yoshihide FujiyamaAbstract:Abstract Objective SelenoProtein-P is a selenium-rich serum Protein that carries more than 50% of serum selenium. We evaluated changes in serum SelenoProtein-P levels in Patients with inflammatory bowel disease. Methods Serum SelenoProtein-P levels were measured by enzyme-linked immunosorbent assay. Twenty healthy individuals (controls), 34 Patients with ulcerative colitis, and 37 Patients with Crohn’s disease (CD) were studied. Results A highly significant correlation was found between the serum selenium and SelenoProtein-P levels. There was no significant difference in serum SelenoProtein-P levels between healthy controls (average 3.4 ± 0.8 μg/mL, n = 20) and Patients with ulcerative colitis (3.0 ± 1.0 μg/mL, n = 34). Serum SelenoProtein-P levels were significantly lower in Patients with CD (average 1.8 ± 0.5 μg/mL, n = 37). Serum SelenoProtein-P levels were significantly lower in the elemental diet grouP of Patients who had CD (average 1.4 ± 0.4 μg/mL, n = 17) than in the non-elemental diet grouP of Patients who had CD (average 2.1 ± 0.3 μg/mL, n = 20). Conclusion We found that the serum SelenoProtein-P level is decreased in Patients with CD. It may be a useful marker to monitor the systemic selenium status in various disorders.
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SelenoProtein P as a Predictor for evaluating gemcitabine resistance in human Pancreatic cancer cells
International Journal of Cancer, 2004Co-Authors: Shin Ichiro Maehara, Yoshiro Saito, Kazuhiko Takahashi, Shinji Tanaka, Mitsuo Shimada, Ken Shirabe, Yoshihiko MaeharaAbstract:Gemcitabine is a new standard chemotheraPeutic agent used in the treatment of Pancreatic cancer, but the mechanisms of gemcitabine sensitivity are still controversial. In our study to determine a mechanism that regulates gemcitabine sensitivity, we carried out molecular analysis on the suscePtibility of the Pancreatic cancer cells. Using a gemcitabinesensitive Pancreatic cancer cell line KLM1, we established a resistant cell line KLM1-R exhibiting a 20-fold IC50-value (the concentration of gemcitabine causing 50% growth inhibition). Microarray analysis of genes showed sPecific exPression of SelenoProtein P, one of the anti-oxidants, in the KLM1-R cell line but not in the KLM1 cell line. Administration of SelenoProtein P inhibited the gemcitabine-induced cytotoxicity in the Pancreatic cell lines. The levels of intracellular reactive oxygen sPecies (ROS) were increased in the KLM1 cells by gemcitabine, but SelenoProtein P suPPressed the gemcitabine-induced ROS levels. Furthermore interferon- suPPressed the exPression of SelenoProtein P mRNA and increased intracellular ROS level, leading to the recovery of the gemcitabine sensitivity in KLM1-R. These results suggest a novel mechanism that SelenoProtein P reduces the intracellular ROS levels, resulting in the insuscePtibility to gemcitabine. © 2004 Wiley-Liss, Inc.
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domain structure of bi functional SelenoProtein P
Biochemical Journal, 2004Co-Authors: Yoshiro Saito, Masaki Hirashima, Gen Takebe, Shigeharu Nagasawa, Noriko Sato, Kazuhiko TakahashiAbstract:Human SelenoProtein P (SeP), a selenium-rich Plasma glycoProtein, is Presumed to contain ten selenocysteine residues; one of which is located at the 40th residue in the N-terminal region and the remaining nine localized in the C-terminal third Part. We have shown that SeP not only catalyses the reduction of PhosPhatidylcholine hydroPeroxide by glutathione [Saito, Hayashi, Tanaka, Watanabe, Suzuki, Saito and Takahashi (1999) J. Biol. Chem. 274, 2866-2871], but also suPPlies its selenium to Proliferating cells [Saito and Takahashi (2002) Eur. J. Biochem. 269, 5746-5751]. Treatment of SeP with Plasma kallikrein resulted in a sequential limited Proteolysis (Arg-235-Gln-236 and Arg-242-AsP-243). The N-terminal (residues 1-235) and C-terminal (residues 243-361) fragments exhibited enzyme activity and selenium-suPPly activity resPectively. These results confirm that SeP is a bi-functional Protein and suggest that the first selenocysteine residue is the active site of the enzyme and the remaining nine residues function as a selenium suPPlier.