Generic placeholder image

Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article (Mini-Review)

Trans-sialidase Associated with Atherosclerosis: Defining the Identity of a Key Enzyme Involved in the Pathology

Author(s): Victor Y. Glanz, Veronika A. Myasoedova, Andrey V. Grechko and Alexander N. Orekhov*

Volume 20 , Issue 9 , 2019

Page: [938 - 941] Pages: 4

DOI: 10.2174/1389450120666190308111619

Price: $65


Atherosclerosis is associated with the increased trans-sialidase activity, which can be detected in the blood plasma of atherosclerosis patients. The likely involvement in the disease pathogenesis made this activity an interesting research subject and the enzyme that may perform such activity was isolated and characterized in terms of substrate specificity and enzymatic properties. It was found that the enzyme has distinct optimum pH values, and its activity was enhanced by the presence of Ca2+ ions. Most importantly, the enzyme was able to cause atherogenic modification of lowdensity lipoprotein (LDL) particles in vitro. However, the identity of the discovered enzyme remained to be defined. Currently, sialyltransferases, mainly ST6Gal I, are regarded as major contributors to sialic acid metabolism in human blood. In this mini-review, we discuss the possibility that atherosclerosis- associated trans-sialidase does, in fact, belong to the sialyltransferases family.

Keywords: Trans-sialidase, sialic acid, sialyltransferase, atherosclerosis, blood plasma, circulation.

Graphical Abstract
Alipov V, Sukhorukov V, Karagodin V, Grechko A, Orekhov A. Chemical composition of circulating native and desialylated low density lipoprotein: what is the difference? Vessel Plus 2017; 1: 107-15.
Tertov VV, Kaplun VV, Sobenin IA, Boytsova EY, Bovin NV, Orekhov AN. Human plasma trans-sialidase causes atherogenic modification of low density lipoprotein. Atherosclerosis 2001; 159(1): 103-15.
[] [PMID: 11689212]
Tertov VV, Nikonova EY, Nifant’ev NE, Bovin NV, Orekhov AN. Human plasma trans-sialidase donor and acceptor specificity. Biochemistry (Mosc) 2002; 67(8): 908-13.
[] [PMID: 12223090]
Nikonova EY, Tertov VV, Sato C, Kitajima K, Bovin NV. Specificity of human trans-sialidase as probed with gangliosides. Bioorg Med Chem Lett 2014; 14: 5161-4.
Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, Samyn-Petit B, Julien S, Delannoy P. The human sialyltransferase family. Biochimie 2001; 83: 727-37.
Noel M, Gilormini P-A, Cogez V, et al. Probing the CMP-Sialic Acid Donor Specificity of Two Human β-d-Galactoside Sialyltransferases (ST3Gal I and ST6Gal I) Selectively Acting on O- and N-Glycosylproteins. ChemBioChem 2017; 18(13): 1251-9.
[] [PMID: 28395125]
Williams MA, Kitagawa H, Datta AK, Paulson JC, Jamieson JC. Large-scale expression of recombinant sialyltransferases and comparison of their kinetic properties with native enzymes. Glycoconj J 1995; 12(6): 755-61. 8748151
[] [PMID: 8748151]
Bhide GP, Colley KJ. Sialylation of N-glycans: mechanism, cellular compartmentalization and function. Histochem Cell Biol 2017; 147(2): 149-74.
[] [PMID: 27975143]
Tailford LE, Owen CD, Walshaw J, et al. Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation. Nat Commun 2015; 6: 7624.
[] [PMID: 26154892]
Takashima S. Characterization of mouse sialyltransferase genes: their evolution and diversity. Biosci Biotechnol Biochem 2008; 72(5): 1155-67.
[] [PMID: 18460788]
Harduin-Lepers A. Comprehensive analysis of sialyltransferases in vertebrate genomes. Glycobiol Insights 2010; 2: 29-61.
Song J, Xue C, Preisser JS, et al. Association of single nucleotide polymorphisms in the ST3GAL4 Gene with VWF antigen and factor VIII activity. PLoS One 2016; 11(9): e0160757.
[] [PMID: 27584569]
Audry M, Jeanneau C, Imberty A, Harduin-Lepers A, Delannoy P, Breton C. Current trends in the structure-activity relationships of sialyltransferases. Glycobiology 2011; 21(6): 716-26.
[] [PMID: 21098518]
Gracheva EV, Samovilova NN, Golovanova NK. Il′inskaya OP, Tararak EM, Malyshev PP, Kukharchuk VV, Prokazova NV. Sialyltransferase activity of human plasma and aortic intima is enhanced in atherosclerosis. Biochim Biophys Acta Mol Basis Dis 2002; 1586: 123-8.
[ 00093-X]
Jones MB, Nasirikenari M, Lugade AA, Thanavala Y, Lau JTY. Anti-inflammatory IgG production requires functional P1 promoter in β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) gene. J Biol Chem 2012; 287(19): 15365-70.
[] [PMID: 22427662]
Jones MB, Nasirikenari M, Feng L, et al. Role for hepatic and circulatory ST6Gal-1 sialyltransferase in regulating myelopoiesis. J Biol Chem 2010; 285(32): 25009-17.
[ 10.1074/jbc.M110.104406] [PMID: 20529847]
Dougher CWL, Buffone A Jr, Nemeth MJ, et al. The blood-borne sialyltransferase ST6Gal-1 is a negative systemic regulator of granulopoiesis. J Leukoc Biol 2017; 102(2): 507-16.
[] [PMID: 28550122]
Datta AK. Comparative sequence analysis in the sialyltransferase protein family: analysis of motifs. Curr Drug Targets 2009; 10(6): 483-98.
[] [PMID: 19519350]
Zhang J, Liu Y, Deng X, Chen L, Yang X, Yu C. ST6GAL1 negatively regulates monocyte transendothelial migration and atherosclerosis development. Biochem Biophys Res Commun 2018; 500(2): 249-55.
[] [PMID: 29654763]
Sugimoto I, Futakawa S, Oka R, et al. Beta-galactoside alpha2,6-sialyltransferase I cleavage by BACE1 enhances the sialylation of soluble glycoproteins. A novel regulatory mechanism for alpha2,6-sialylation. J Biol Chem 2007; 282(48): 34896-903.
[] [PMID: 17897958]
Deng X, Zhang J, Liu Y, Chen L, Yu C. TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1. Sci Rep 2017; 7: 40256.
[] [PMID: 28091531]
Sabarinath PS, Appukuttan PS. Immunopathology of desialylation: human plasma lipoprotein(a) and circulating anti-carbohydrate antibodies form immune complexes that recognize host cells. Mol Cell Biochem 2015; 403(1-2): 13-23.
[] [PMID: 25633186]
Bork K, Weidemann W, Berneck B, et al. The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids. Gene Expr Patterns 2017; 23-24: 52-8.
[] [PMID: 28351515]
Mondal N, Buffone A Jr, Stolfa G, et al. ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes. Blood 2015; 125(4): 687-96.
[] [PMID: 25498912]
Lee MM, Nasirikenari M, Manhardt CT, et al. Platelets support extracellular sialylation by supplying the sugar donor substrate. J Biol Chem 2014; 289(13): 8742-8.
[ C113.546713] [PMID: 24550397]
Lee-Sundlov MM, Ashline DJ, Hanneman AJ, et al. Circulating blood and platelets supply glycosyltransferases that enable extrinsic extracellular glycosylation. Glycobiology 2017; 27: 188-98.
Döring Y, Noels H, Mandl M, et al. Deficiency of the sialyltransferase St3Gal4 reduces Ccl5-mediated myeloid cell recruitment and arrest: short communication. Circ Res 2014; 114(6): 976-81.
[] [PMID: 24425712]
Pu Q, Yu C. Glycosyltransferases, glycosylation and atherosclerosis. Glycoconj J 2014; 31(9): 605-11.
[] [PMID: 25294497]
Mehr K, Withers SG. Mechanisms of the sialidase and trans-sialidase activities of bacterial sialyltransferases from glycosyltransferase family 80. Glycobiology 2016; 26(4): 353-9.
[] [PMID: 26582604]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy