Abstract
Selenoprotein P (SELENOP) is a serum glycoprotein that is required for proper selenium distribution in mammals, particularly in supplying selenium to the brain and testes. As the sole mechanism for providing essential selenium to developing spermatozoa, SELENOP metabolism is central to male fertility in all mammals. In addition, this process is important for proper brain function, especially under conditions of limited dietary selenium. Several specific and nonspecific mechanisms for SELENOP uptake in target tissues have been described, but the utilization of SELENOP as a source of selenium for intracellular selenoprotein production has not been systematically characterized. In this report, we examine the process of SELENOP uptake using a robust selenium uptake assay that measures selenium utilization in cells fed 75Se-SELENOP. Using a series of inhibitors and modulators we have identified specific regulators of the process and found that SELENOP must be in an oxidized state for uptake. This assay also demonstrates that SELENOP uptake is not highly sequence specific as the zebrafish protein is recognized and processed by mammalian cells.
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Burk RF, Gregory PE (1982) Some characteristics of 75Se-P, a selenoprotein found in rat liver and plasma, and comparison of it with selenoglutathione peroxidase. Arch Biochem Biophys 213(1):73–80
Motsenbocker MA, Tappel AL (1982) A selenocysteine-containing selenium-transport protein in rat plasma. Biochim Biophys Acta 719(1):147–153
Motchnik PA, Tappel AL (1990) Multiple selenocysteine content of selenoprotein P in rats. J Inorg Biochem 40(3):265–269
Hill KE, Lloyd RS, Yang JG, Read R, Burk RF (1991) The cDNA for rat selenoprotein P contains 10 TGA codons in the open reading frame. J Biol Chem 266(16):10050–10053
Hill KE, Zhou J, McMahan WJ, Motley AK, Atkins JF, Gesteland RF, Burk RF (2003) Deletion of selenoprotein P alters distribution of selenium in the mouse. J Biol Chem 278(16):13640–13646. doi:10.1074/jbc.M300755200
Schomburg L, Schweizer U, Holtmann B, Flohé L, Sendtner M, Köhrle J (2003) Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. Biochem J 370(Pt 2):397–402. doi:10.1042/BJ20021853
Pitts MW, Raman AV, Hashimoto AC, Todorovic C, Nichols RA, Berry MJ (2012) Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating. Neuroscience:20858–20868. doi:10.1016/j.neuroscience.2012.02.017
Jackson-Rosario S, Cowart D, Myers A, Tarrien R, Levine RL, Scott RA, Self WT (2009) Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct. J Biol Inorg Chem 14(4):507–519. doi:10.1007/s00775-009-0466-z
Caito SW, Milatovic D, Hill KE, Aschner M, Burk RF, Valentine WM (2011) Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted. Brain Res:13981–13912. doi:10.1016/j.brainres.2011.04.046
Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, Flohé L (1999) Dual function of the selenoprotein PHGPx during sperm maturation. Science 285(5432):1393–1396
Olson GE, Winfrey VP, Hill KE, Burk RF (2008) Megalin mediates selenoprotein P uptake by kidney proximal tubule epithelial cells. J Biol Chem 283(11):6854–6860. doi:10.1074/jbc.M709945200
Olson GE, Winfrey VP, Nagdas SK, Hill KE, Burk RF, Apolipoprotein E (2007) Receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J Biol Chem 282(16):12290–12297. doi:10.1074/jbc.M611403200
Burk RF, Olson GE, Hill KE, Winfrey VP, Motley AK, Kurokawa S (2013) Maternal-fetal transfer of selenium in the mouse. FASEB J. doi:10.1096/fj.13-231852
Kurokawa S, Hill KE, McDonald WH, Burk RF (2012) Long isoform mouse selenoprotein P (Sepp1) supplies rat myoblast L8 cells with selenium via endocytosis mediated by heparin binding properties and apolipoprotein E receptor-2 (ApoER2). J Biol Chem 287(34):28717–28726. doi:10.1074/jbc.M112.383521
Burk RF, Hill KE, Read R (1991) Bellew T response of rat selenoprotein P to selenium administration and fate of its selenium. Am J Phys 261(1 Pt 1):E26–E30
Raman AV, Pitts MW, Seyedali A, Hashimoto AC, Seale LA, Bellinger FP, Berry MJ (2012) Absence of selenoprotein P but not selenocysteine lyase results in severe neurological dysfunction. Genes Brain Behav 11(5):601–613. doi:10.1111/j.1601-183X.2012.00794.x
Méplan C, Nicol F, Burtle BT, Crosley LK, Arthur JR, Mathers JC, Hesketh JE (2009) Relative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer status. Antioxid Redox Signal 11(11):2631–2640. doi:10.1089/ARS.2009.2533
Suzuki KT, Shiobara Y, Itoh M (1998) Ohmichi M selective uptake of selenite by red blood cells. Analyst 123(1):63–67
Ganyc D, Self WT (2008) High affinity selenium uptake in a keratinocyte model. FEBS Lett 582(2):299–304. doi:10.1016/j.febslet.2007.12.022
Ma S, Hill KE, Burk RF, Caprioli RM (2005) Mass spectrometric determination of selenenylsulfide linkages in rat selenoprotein P. J Mass Spectrom 40(3):400–404. doi:10.1002/jms.801
Gromer S, Arscott LD, Williams CH, Schirmer RH, Becker K (1998) Human placenta thioredoxin reductase. Isolation of the selenoenzyme, steady state kinetics, and inhibition by therapeutic gold compounds. J Biol Chem 273(32):20096–20101
Crane MS, Howie AF, Arthur JR, Nicol F, Crosley LK, Beckett GJ (2009) Modulation of thioredoxin reductase-2 expression in EAhy926 cells: implications for endothelial selenoprotein hierarchy. Biochim Biophys Acta 1790(10):1191–1197. doi:10.1016/j.bbagen.2009.07.001
Kurokawa S, Bellinger FP, Hill KE, Burk RF, Berry MJ (2014) Isoform-specific binding of selenoprotein P to the β-propeller domain of apolipoprotein E receptor 2 mediates selenium supply. J Biol Chem 289(13):9195–9207. doi:10.1074/jbc.M114.549014
Acknowledgements
Thanks to Mark Pinkerton for critical reading of this manuscript. This work was supported by the National Institutes of Health (NIH R01-GM077073 and R21HD083616) and the Found Animals Foundation, Los Angeles, CA (D0910-W11).
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Shetty, S., Marsicano, J.R. & Copeland, P.R. Uptake and Utilization of Selenium from Selenoprotein P. Biol Trace Elem Res 181, 54–61 (2018). https://doi.org/10.1007/s12011-017-1044-9
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DOI: https://doi.org/10.1007/s12011-017-1044-9