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Characterization and Quantification of Selenoprotein P

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Characterization and Quantification of Selenoprotein P International Journal of Molecular Sciences Review Characterization and Quantification of Selenoprotein P: Challenges to Mass Spectrometry Jérémy Lamarche 1,* , Luisa Ronga 1, Joanna Szpunar 1 and Ryszard Lobinski 1,2,3 1 IPREM UMR5254, E2S UPPA, Institut des Sciences Analytiques et de Physico-Chimie Pour l’Environnement et les Matériaux, CNRS, Université de Pau et des Pays de l’Adour, Hélioparc, 64053 Pau, France; [email protected] (L.R.); [email protected] (J.S.); [email protected] (R.L.) 2 World-Class Research Center “Digital Biodesign and Personalized Healthcare”, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia 3 Chair of Analytical Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland * Correspondence: [email protected] Abstract: Selenoprotein P (SELENOP) is an emerging marker of the nutritional status of selenium and of various diseases, however, its chemical characteristics still need to be investigated and methods for its accurate quantitation improved. SELENOP is unique among selenoproteins, as it contains multiple genetically encoded SeCys residues, whereas all the other characterized selenoproteins contain just one. SELENOP occurs in the form of multiple isoforms, truncated species and post-translationally modified variants which are relatively poorly characterized. The accurate quantification of SELENOP is contingent on the availability of specific primary standards and reference methods. Before recom- binant SELENOP becomes available to be used as a primary standard, careful investigation of the characteristics of the SELENOP measured by electrospray MS and strict control of the recoveries at the various steps of the analytical procedures are strongly recommended. This review critically discusses the state-of-the-art of analytical approaches to the characterization and quantification of SE- Citation: Lamarche, J.; Ronga, L.; Szpunar, J.; Lobinski, R. LENOP. While immunoassays remain the standard for the determination of human and animal health Characterization and Quantification status, because of their speed and simplicity, mass spectrometry techniques offer many attractive and of Selenoprotein P: Challenges to complementary features that are highlighted and critically evaluated. Mass Spectrometry. Int. J. Mol. Sci. 2021, 22, 6283. https://doi.org/ Keywords: selenoprotein P; mass spectrometry; metrology; selenium; cancer; biomarker; selenocysteine 10.3390/ijms22126283 Academic Editor: Antonella Roveri 1. Introduction Received: 4 May 2021 Selenium, originally known for its toxicity, was subsequently recognized as an es- Accepted: 7 June 2021 sential trace element [1] and has been increasingly marketed as a life-style drug [2]. The Published: 11 June 2021 importance of Se is related to its antioxidant properties, its role in the endocrine and im- mune system, as well as its involvement in the protection against certain diseases, such Publisher’s Note: MDPI stays neutral as cancer, diabetes, cardiovascular or immune system disorders [3]. The narrow range of with regard to jurisdictional claims in the optimum selenium concentration in biological fluids, the multiplicity of its chemical published maps and institutional affil- iations. forms and the diversity of its biological activities are driving interest for precise molecular markers of its status in various organisms. The activity of Se is mainly mediated by selenoproteins. They contain in their se- quence at least one selenocysteine (SeCys, U), which is genetically encoded and often referred to as the 21st amino-acid [4]. In the presence of a specific stemloop RNA sequence Copyright: © 2021 by the authors. element (SECIS), the UGA codon, normally acting as a stop codon to terminate translation, Licensee MDPI, Basel, Switzerland. codes for the insertion of SeCys into a polypeptide chain [2,5]. The pioneering works of This article is an open access article Gladyshev group [6,7] started the development of algorithms predicting the existence of distributed under the terms and conditions of the Creative Commons many selenoproteins in different biological species [8,9]. The number of selenoproteins Attribution (CC BY) license (https:// that can be expressed in different organisms varies, ranging from 1 in certain insects, to creativecommons.org/licenses/by/ 9 in common spider, 25 in humans [10], and 32 in oysters [11]. In vertebrates, the mRNA 4.0/). Int. J. Mol. Sci. 2021, 22, 6283. https://doi.org/10.3390/ijms22126283 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 23 Int. J. Mol. Sci. 2021, 22, 6283 2 of 23 in common spider, 25 in humans [10], and 32 in oysters [11]. In vertebrates, the mRNA encoding SELENOPencoding is distinct SELENOP from isthat distinct encoding from other that encodingselenoproteins, other selenoproteins,in that it contains in that it contains two SECIS elementstwo SECIS instead elements of one [12] instead. of one [12]. Selenoprotein PSelenoprotein is unique amongst P is uniqueall the characterized amongst all selenoproteins the characterized in that selenoproteins it con- in that it tains multiple SeCyscontains residues multiple, whereas SeCys residues,all other whereasselenoproteins all other contain selenoproteins only one contain SeCys. only one SeCys. The number of TheSeCys number residues of SeCysin SELENOP residues from in SELENOP different organisms from different varies organisms (Figure 1), varies (Figure1), amounting to 10amounting for humans, to 1046 forin oysters humans, [11] 46 and in oysters 132 in [one11]- andspecies 132 bivalve in one-speciess [13]. bivalves [13]. FigureFigure 1. Putative1. Putative number number of SeCys of SeCys residues residues in SELENOP in SELENOP in different in different organisms organisms (according (according to [11,12 to,14 ]). [11,12,14]). SELENOP was first reported in 1973 by Burk et al. [15] and Rotruck et al. [16]. Mc- SELENOP Connellwas first et al.reported [17] and in Motsenbocker 1973 by Burk et et al. al. [18 ][15] found and that Rotruck SELENOP et al. was [16] synthetized. in the McConnell et al.liver [17] of and rats Motsenbocker and secreted intoet al. the [18] plasma. found A that few SELENOP years later, was the synthetized existence of SELENOP was in the liver of ratconfirmeds and secreted in humans, into the where plasma. it is consideredA few years as later, a valuable the existence marker of for SELE- nutritional selenium NOP was confirmedstatus in [ 19humans]. In 2016,, where Gladyshev it is considered et al. proposed as a valuable a non-ambiguous marker for nutritional notation for all seleno- selenium statusproteins [19]. In 2016, using Gladyshev the root symbol et al. proposed SELENO followeda non-ambiguous by a letter, notation leading for to theall creation of the selenoproteins usingabbreviation the root SELENOP symbol SELENO for selenoprotein followed by P, replacinga letter, leading the previously to the creation used as abbreviations of the abbreviationsuch SELENOP as SeP, SEEP1, for selenop SelP [rotein20]. Expression, P, replacing functions the previously and role used of as SELENOP abbre- in mammals viations such aswere SeP, reviewed SEEP1, SelP [21]. [20]. Expression, functions and role of SELENOP in mammals were reviewedAs a biomarker,[21]. SELENOP can discriminate between the specific and nonspecific As a biomarker,(and therefore SELENOP non-significant) can discriminate incorporation between the of Sespecific in proteins and non [22specific,23]. It responds to Se (and therefore nonsupplementation-significant) incorporation over a wider of range Se in of proteins intakes [22,23] than GPx3. It responds [24]. In marginallyto Se supplied supplementationindividuals, over a wider low range serum of Se intakes was found than to GPx3 be mirrored [24]. In bymarginally the circulating supplied SELENOP concen- individuals, lowtration, serum butSe was not found by the to GPx3 be mirrored activity by [25 the]. In circulating studies of SELENOP populations concen- with relatively low tration, but notselenium by the GPx3 intakes, activity SELENOP [25]. In was studies found of to populations respond to different with relatively dietary seleniumlow forms [26]. selenium intakes,Serum SELENOP SELENOP was concentration found to respond can be to more different than a dietary biomarker selenium of Se status: forms it was proposed [26]. Serum SELENOPto be used concentration for the diagnosis can be and more assessment than a biomarker of treatment of efficacySe status: and it long-term was prognosis proposed to be inused patients for the with diagnosis pulmonary and assessment arterial hypertension of treatment [efficacy27] and and hypertension long-term [28]. Recently, prognosis in patientsthe mortality with pulmonary risk from COVID-19arterial hypertension was shown [27] to be and associated hypertension with selenium[28]. deficiency, and more specifically with SELENOP deficiency, causing a dysregulation of the redox Recently, the mortality risk from COVID-19 was shown to be associated with selenium homeostasis in pathological conditions which resulted in an excessive reactive oxygen deficiency, and more specifically with SELENOP deficiency, causing a dysregulation of species (ROS) generation [29,30]. the redox homeostasis in pathological conditions which resulted in an excessive reactive During the last 40 years, many functions have been attributed to SELENOP including oxygen species (ROS) generation [29,30]. its involvement in the storage of selenium
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