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Antigenic Mimicry in Neisseria Species
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Peter C. Giardina, Michael A. Apicella, Brad Gibson, Andrew Preston
LOS mimicry of human glycolipid precursors suggested that host enzymes might modify bacterial LOS in vivo. Mandrell and coworkers identified two mammalian sialyltransferases, rat liver CMP-NANA: Galβ(1→4)GlcNAcα(2→6) sialyltransferase and porcine submaxillary gland CMP-NANA: Galα(2→3) sialyltransferase, that incorporated sialic acid into LOS, however, sialic acid was incorporated into other bacterial molecules not sialylated by the putative bacterial sialyltransferase (39). These results suggested that exogenous LOS sialylation by host-derived sialyltransferase(s) might occur if the substrates CMP-NANA and bacterial LOS co-localize with host-derived sialyltransferase during infection.
Inherited Differences in Alpha1-Antitrypsin
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
It has been mentioned before that the Ζ variant has a lower net negative electric charge [65], This variant has, in fact, the lowest negative charge that has been found to date; the last letter of the alphabet for this variant is therefore quite appropriate. Early speculations suggested that sialic acid and perhaps part of a carbohydrate side chain were missing from Ζ protein and that this was the reason for its lower charge [77]. This idea was based on the observation that treatment of normal M alpha1-antitrypsin with neuraminidase produced a protein with lower electrophoretic mobility similar to Ζ [77,78]. Results of chemical analysis of the carbohydrates of alpha1-antitrypsin are discussed below. The suggestion that sialyltransferase had a low serum concentration in persons with alpha1-antitrypsin deficiency [79] has also been made but there is no experimental support [80] for this premise.
Defects in Tg Gene Expression and Tg Secretion
Published in Geraldo Medeiros-Neto, John Bruton Stanbury, Inherited Disorders of the Thyroid System, 2019
Geraldo Medeiros-Neto, John Bruton Stanbury
Further studies on the thyroid tissue of one affected sib of this family (JBM) were conducted by Grollman et al.127 Hydrolysis of the purified Tg indicated that practically all of the radioactivity was present as mono- and diiodotyrosines. The yield of T4 was fivefold less than normal. When the carbohydrates of normal and defective Tg were analyzed there was no difference in glucosamine, galactose, or mannose, but unlike normal Tg that had a mean sialic content of 7.3 μg/mg protein the defective Tg had a sialic acid concentration of only 0.3 μg/mg protein. Sialic acid could be incorporated into the defective Tg using sialyltransferase from rat liver. No sialyltransferase activity was detectable in a homogenate of the goiter tissue, although it was readily demonstrated in homogenates from other normal glands and in specimens of endemic goiter. Thus, the lack of sialic acid in the defective Tg could be explained by a deficiency in sialyltransferase rather than an abnormal acceptor protein. Severely hyposialylated Tg is probably linked to a defect in iodotyrosine coupling and to abnormal migration of Tg into the follicular lumen.
A glyco-engineering approach for site-specific conjugation to Fab glycans
Published in mAbs, 2023
Maria L. Jaramillo, Traian Sulea, Yves Durocher, Mauro Acchione, Melissa J. Schur, Anna Robotham, John F. Kelly, Marie-France Goneau, Alma Robert, Yuneivy Cepero-Donates, Michel Gilbert
More recent approaches involve enzymatic remodeling of the N-glycans in order to introduce a bioorthogonal reactive group under mild conditions. Wild-type (WT) or mutant glycosyltransferases can be used to add modified sugar residues to the termini of existing N-glycan “branches”. When terminal GlcNAc residues are available, it is possible to add functionalized galactose or N-acetylgalactosamine residues using a mutant form (Y289L) of the β-1,4-galactosyltransferase I (B4GalT1) and subsequently conjugate a cytotoxic payload.12–14 The ST6 β-galactoside α-2,6-sialyltransferase 1 (ST6Gal1) can be used to transfer functionalized sialic acid to N-glycans. Li et al. incorporated 9-azido-N-acetylneuraminic acid to the Fc glycans of an anti-CD22 mAb and attached various labels and a cytotoxic drug by strain-promoted azide-alkyne cycloaddition.15
Circulating platelets supply ST6Gal-1 in patients with IgA nephropathy
Published in Postgraduate Medicine, 2023
Youxia Liu, Hongshan Chen, Hongfen Li, Fanghao Wang, Junya Jia, Tiekun Yan
ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates [7,8]. ST6Gal-1 is reported to be associated with pathological states, including malignancies and inflammatory conditions [9–12]. A previous genome-wide association study (GWAS) which was performed in the Chinese Han population identified the risk allele C at rs7634389 at the ST6GAL1 locus was associated with the susceptibility of IgAN [13]. It was demonstrated that the level of ST6GAL1 mRNA was significantly increased in the plasma of IgAN patients [14]. Our previous study showed ST6Gal-1 levels in plasma were elevated in patients with IgAN and associated with a slower progression of IgAN [15]. ST6Gal-1 can freely circulate in the plasma, however, the origin of this blood-borne glycan-modifying enzyme has remained enigmatic.
Effects of hypertension and FAAH inhibitor treatment of rats with primary and secondary hypertension considering the physicochemical properties of erythrocytes
Published in Toxicology Mechanisms and Methods, 2020
Izabela Dobrzyńska, Barbara Szachowicz-Petelska, Anna Pędzińska-Betiuk, Zbigniew A. Figaszewski, Elżbieta Skrzydlewska
This study showed that administration of the FAAH inhibitor URB597 to hypertensive rats reduced the levels of lipid peroxidation products and increased those of phospholipids on erythrocyte membranes. With increasing amounts of phospholipids, the numbers of negatively and positively charged functional groups increased, increasing the total CTA concentration and changing the constants of KAH and KBOH. URB597 administration to rats with primary and secondary hypertension also reduced the plasma sialic acid content, due to release from the erythrocyte membrane. This may be due to changes in the activity of enzymes responsible for the incorporation of sialyl acid residues (sialyltransferase) and removal of sialic acid residues (sialidase) (Chiarini et al. 1993; Hadengue et al. 1998). An increase in the amount of sialic acid in the membrane leads to increased negative electrical charge on the membrane surface, as well as intracellular electrostatic repulsion, which results in reduced aggregation of erythrocytes. The increased sialic acid content corresponded to the surface charge density and led to changes in the zeta potential and values of membrane characteristics such as CTA, as well as KAH and KBOH. These modifications affect, among other things, membrane permeability, transport systems and receptor functions (Cerecedo et al. 2016; Kloza et al. 2017; Polak et al. 2018).