Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.7 (sialyltransferase)
 1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduction of pig cell-surface alpha-galactosyl (Gal) epitope, Galalpha1, 3Galbeta1, 4GlcNAc-R, by the introduction of glycosyltransferase genes is effective in suppressing hyperacute rejection (HAR) in pig-to-human xenotransplantation. The transmission of porcine endogenous retroviruses (PERVs) has been recognized as a potential risk factor associated with xenotransplantation. In this study, effects of the introduction of glycosyltransferase genes to pig cells on the sensitivity of gammaretroviruses to human serum were investigated. Pig endothelial cells (PEC), PEC transduced with alpha1,2 fucosyltransferase (FT), alpha2,3 sialyltransferase (ST), or N-acetylglucosaminyltransferase III (GnT-III), and human embryonic kidney (HEK) 293 cells were transduced with the LacZ gene with the packaging signal of murine leukemia virus (MuLV) under the control of the long terminal repeat of MuLV by a pseudotype infection. Then, the cells were further infected with PERV subtype B (PERV-B) or feline leukemia virus subgroup B (FeLV-B). Culture supernatants of the infected cells were mixed with human serum (HS) and then inoculated to HEK293 cells. The inoculated cells were histochemically stained and lacZ-positive blue foci were counted. Glycosyltransferase activity, xenoantigenicity, and alpha-Gal epitope density in the cells were measured at the time of the infection experiments. PERV-B or FeLV-B particles from the parental PEC were efficiently neutralized by HS, while those from PEC transduced with alpha1,2FT, alpha2,3ST or GnT-III were less sensitive to HS. The transduced PEC exhibited high levels of activity of the introduced glycotransferases, and expressed fewer xenoantigens and cell-surface alpha-Gal epitopes. Our results suggest that gammaretroviruses including PERVs produced by transgenic pigs, that are generally modified to reduce the cell-surface alpha-Gal epitope to overcome the HAR in xenotransplantation, are less sensitive to HS.
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PMID:Sensitivity to human serum of gammaretroviruses produced from pig endothelial cells transduced with glycosyltransferase genes. 1470 22

The rejection caused by the presence of Galalpha1,3Gal (Gal) on the pig vascular endothelium and of natural anti-Gal antibodies in human blood has recently been prevented by the breeding of pigs that do not express Gal, achieved by knocking out the gene for the enzyme, alpha1,3-galactosyltransferase. However, prior to the introduction of nuclear transfer/embryo transfer techniques, a major effort was directed towards reducing Gal expression on pig cells by other methods, such as by cleaving Gal from the underlying substrate, or replacing Gal with an alternative, innocuous oligosaccharide by a process that has been termed 'competitive glycosylation'. Gal has been cleaved by alpha-galactosidase or endo-beta-galactosidase C. Competitive glycosylation has largely targeted replacement of Gal by insertion of a gene for a fucosyltransferase or a sialyltransferase, or by insertions of the gene for N-acetylglucosaminyltransferase III to reduce cell-surface expression of several oligosaccharides. The results of these approaches to render the pig cells less immunogenic to the human immune system are summarized. With regard to the problem provided by Gal expression, the above approaches may be considered by some to be largely obsolete, but the principles underlying them may prove valuable when other antigen targets for human antibodies are definitively identified, if these prove to be carbohydrates.
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PMID:Reducing Gal expression on the pig organ - a retrospective review. 1594 76

N-Glycosylation of proteins is conserved in eukaryotes, which is one of the most abundant post-translational modification reactions, and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharide structure (glycan) are associated with many physiological and pathological events, including cell adhesion, migration, cell growth, cell differentiation and tumor invasion. Glycosylation reactions are catalyzed by the action of glycosyltransferases, which add sugar chains to various glycans on glycoproteins, glycolipids and proteoglycans. Here, we focus mainly on the modification of N-glycans with N-acetylglucosaminyltransferase III (GnT-III), N-acetylglucosaminyltransferase V (GnT-V) and alpha2,6 sialyltransferase (ST6GalI) to address the important roles of N-glycans in integrin-meditaed cell adhesion and migration. In addition, we also discuss the potential roles of N-glycosylation sites on integrin alpha5 subunit.
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PMID:Importance of N-glycosylation on alpha5beta1 integrin for its biological functions. 1942 Jul 42