Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues

Schomburg, Lutz; Schweizer, Ulrich; Holtmann, Bettina; Flohé, Leopold; Sendtner, Michael; Köhrle, Josef

doi:10.1042/bj20021853

Cited by 390 publications

(375 citation statements)

References 31 publications

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“…During the systemic delivery of selenium, selenoprotein P that is present in the plasma is thought to be the selenium supply protein for the biosynthesis of the other selenoproteins including GPxs. 4,5 Recent evidence in selenoprotein P (SelP) knockout mice has shown that the distribution of selenium from the liver to testis and brain is mediated by Sel P. 6,7 It is also found that in the absence of SelP, selenium from selenious acid (SA, H 2 SeO 3 ) in the diet can be distributed to the peripherals by a yet unknown mechanism. 8 So far, little is known about the membrane transport of selenium from selenium source compounds, including SA.…”

Section: Introductionmentioning

confidence: 99%

A thiol-mediated active membrane transport of selenium by erythroid anion exchanger 1 protein

et al. 2012

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In this paper, we describe a thiol-mediated and energy-dependent membrane transport of selenium by erythroid anion exchanger 1 (AE1, also known as band 3 protein). The AE1 is the most abundant integral protein of red cell membranes and plays a critical role in the carbon dioxide transport system in which carbon dioxide is carried as bicarbonate in the plasma. This protein mediates the membrane transport of selenium, an essential antioxidant micronutrient, from red cells to the plasma in a manner that is distinct from the already known anion exchange mechanism. In this pathway, selenium bound to the cysteine 93 of the hemoglobin β chain (Hb-Cysβ93) is transported by the relay mechanism to the Cys317 of the amino-terminal cytoplasmic domain of the AE1 on the basis of the intrinsic interaction between the two proteins and is subsequently exported to the plasma via the Cys843 of the membrane-spanning domain. The selenium export did not occur in plain isotonic buffer solutions and required thiols, such as albumin, in the outer medium. Such a membrane transport mechanism would also participate in the export pathways of the nitric oxide vasodilator activity and other thiol-reactive substances bound to the Hb-Cysβ93 from red cells to the plasma and/or peripherals. 2 IntroductionSelenium belongs to chalcogens that shares similar chemical properties especially with sulfur and, to a lesser extent, with tellurium. This element is an essential micronutrient for humans and other higher animal species. 1 Selenocysteine (SeCys), the 21st naturally occurring amino acid encoded by the UGA codon, is the form of selenium present in enzymes and proteins. In humans, 25 SeCys-containing proteins (selenoproteins) are identified on the basis of their selenoproteome analysis. 2 The best-known selenoproteins are the glutathione peroxidases (GPxs) that can catalyze the reduction of certain peroxide species (R−OOH) to the alcohols (R−OH) at their active center SeCys residue. 1,3 Nutritional selenium is thought to be obtained from a variety of selenium compounds in the diet, mostly in organic forms, such as SeCys and selenomethionine (SeMet). During the systemic delivery of selenium, selenoprotein P that is present in the plasma is thought to be the selenium supply protein for the biosynthesis of the other selenoproteins including GPxs. 4,5 Recent evidence in selenoprotein P (SelP) knockout mice has shown that the distribution of selenium from the liver to testis and brain is mediated by Sel P. 6,7 It is also found that in the absence of SelP, selenium from selenious acid (SA, H 2 SeO 3 ) in the diet can be distributed to the peripherals by a yet unknown mechanism. 8 So far, little is known about the membrane transport of selenium from selenium source compounds, including SA. Inorganic SA is rare as a chemical form of the food source compounds, but highly bioavailable SA is most frequently used as a source compound for the treatment of a selenium deficiency. 9Selenium-enriched yeast (a common form of selenium supplement) is found to contain ...

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Section: Introductionmentioning

confidence: 99%

A thiol-mediated active membrane transport of selenium by erythroid anion exchanger 1 protein

et al. 2012

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“…Initially, we expected profound changes in the thyroid hormone axis, since all three types of iodothyronine-deiodinases (Dio) are selenoenzymes. Surprisingly, no disturbances of Dio activities were observed in liver, kidneys, or brains from our SePP-deficient mice despite decreased activities of other selenoenzymes (19). Even more surprising was the finding that in thyroid, not only Dio1, but also Gpx1 activity of SePP(7/7) mice was not reduced, although brain Gpx1 activity was decreased (Schomburg et al, in revision).…”

Section: Selenoprotein Pmentioning

confidence: 59%

New insights into the physiological actions of selenoproteins from genetically modified mice

Schweizer

Schomburg

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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SummarySelenium (Se) is an essential trace element in mammals. Dietary Se restriction or conditions of Se malabsorption lead to deficiency syndromes or exacerbate established diseases in humans and in many animal models. It is assumed that most, if not all, physiological actions of Se are mediated by selenocysteine (Sec) containing proteins. However, the exact role of particular selenoproteins for certain molecular pathways, for the metabolism of nutrients, hormones or cellular components and for the development and adaptive responses of the organism have often remained elusive. Through the use of transgenic animals, it becomes increasingly feasible to interfere specifically with the expression of single selenoproteins in certain tissues or at certain times. While some transgenic animals exhibit phenotypes that were expected from biochemical studies, in other instances the observed effects were a surprise in view of earlier hypotheses. IUBMB Life, 57: 737 -744, 2005

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“…Total serum Se concentrations were determined by the analytical method involving piazselenol formation and fluorimetric quantification as previously described (10,13). SePP concentrations were measured by the immunoluminometric sandwich assay established recently (9).…”

Section: Methodsmentioning

confidence: 99%

“…SePP concentrations were measured by the immunoluminometric sandwich assay established recently (9). GPx3 activity was determined by the coupled enzymatic assay with t-butylhydroperoxide as substrate (13).…”

Section: Methodsmentioning

confidence: 99%

Selenium Supplementation Fails to Correct the Selenoprotein Synthesis Defect in Subjects with SBP2 Gene Mutations

Schomburg

Dumitrescu

Liao

et al. 2009

Thyroid

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Background: Selenium (Se) is an essential trace element needed for the biosynthesis of selenoproteins. Selenocysteine incorporation sequence binding protein 2 (SBP2) represents a key trans-acting factor for the cotranslational insertion of selenocysteine into selenoproteins. We recently described children with mutations in the SBP2 gene who displayed abnormal thyroid function tests and reduced selenoprotein concentrations. We have tried to improve selenoprotein biosynthesis and thyroid hormone metabolism in SBP2 deficient subjects by supplementing an organic and an inorganic Se form. Methods: Three affected and two unaffected siblings received daily doses of 100, 200, or 400 mg selenomethionine-rich yeast and 400 mg sodium selenite for one month each. Serum was drawn at baseline and after supplementations. Thyroid function tests, extracellular glutathione peroxidase activity, Se, and selenoprotein P concentrations were determined. Results: Selenomethionine-rich yeast increased serum Se concentrations in all subjects irrespective of genotype. Sodium selenite was effective in increasing the selenoprotein P concentration in normal and to a lesser degree in affected subjects. Both forms failed to increase the glutathione peroxidase activity or to correct the thyroid function abnormalities in the SBP2 deficient individuals indicating that impaired deiodinase expression was not positively affected. No adverse side effects were observed. Conclusions: Total serum Se concentrations in SBP2 deficient subjects respond to selenomethionine supplementation but this effect is not indicative for improved selenoprotein synthesis. Se is obviously not a limiting factor in the SBP2 deficient individuals when regular daily Se intake is provided. These findings might help to identify and diagnose more individuals with selenoprotein biosynthesis defects who might present at young age irrespective of their Se supply with characteristic thyroid function test abnormalities, growth retardation, and reduced Se and selenoprotein concentrations.

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Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues

Cited by 390 publications

References 31 publications

A thiol-mediated active membrane transport of selenium by erythroid anion exchanger 1 protein

A thiol-mediated active membrane transport of selenium by erythroid anion exchanger 1 protein

New insights into the physiological actions of selenoproteins from genetically modified mice

Selenium Supplementation Fails to Correct the Selenoprotein Synthesis Defect in Subjects with SBP2 Gene Mutations

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