ST6GAL1
Beta-galactoside alpha-2,6-sialyltransferase 1 (EC 2.4.99.1) (Alpha 2,6-ST 1) (B-cell antigen CD75) (CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,6-sialyltransferase 1) (ST6Gal I) (ST6GalI) (Sialyltransferase 1) [SIAT1]
PublicationsПравить
Glycosylation is one of the most frequent post-translational modification of proteins. Many membrane and secreted proteins are decorated by sugar chains mainly linked to asparagine (N-linked) or to serine or threonine (O-linked). The biosynthesis of the sugar chains is mainly controlled by the activity of their biosynthetic enzymes: the glycosyltransferases. Glycosylation plays multiple roles, including the fine regulation of the biological activity of glycoproteins. Inflammaging is a chronic low grade inflammatory status associated with aging, probably caused by the continuous exposure of the immune system to inflammatory stimuli of endogenous and exogenous origin. The aging-associated glycosylation changes often resemble those observed in inflammatory conditions. One of the most reproducible markers of calendar and biological aging is the presence of N-glycans lacking terminal galactose residues linked to Asn of IgG heavy chains (IgG-G0). Although the mechanism(s) generating IgG-G0 remain unclear, their presence in a variety of inflammatory conditions suggests a link with inflammaging. In addition, these aberrantly glycosylated IgG can exert a pro-inflammatory effect through different mechanisms, triggering a self-fueling inflammatory loop. A strong association with aging has been documented also for the plasmatic forms of glycosyltrasferases B4GALT1 and ST6GAL1, although their role in the extracellular glycosylation of antibodies does not appear likely. Siglecs, are a group of sialic acid binding mammalian lectins which mainly act as inhibitory receptors on the surface of immune cells. In general activity of Siglecs appears to be associated with long life, probably because of their ability to restrain aging-associated inflammation.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Glycomics
- Glycoproteins
- Glycosylation
- Inflammation
Keywords
- Glycosylation in aging
- Hypogalactosylated antibodies
- Inflammaging
- Plasmatic glycosyltransferases
- Siglecs
The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N-acetylglucosamine (IgG-G0) whose biogenesis has not been fully explained. Although the biosynthesis of glycans is in general mediated by glycosyltransferases associated with internal cell membranes, the extracellular glycosylation of circulating glycoproteins mediated by plasmatic glycosyltransferases has been recently demonstrated. In this study we have investigated the relationship between plasmatic glycosyltransferases, IgG glycosylation and inflammatory and aging markers. In cohorts of individuals ranging from infancy to centenarians we determined the activity of plasmatic β4 galactosyltransferase(s) (B4GALTs) and of α2,6-sialyltransferase ST6GAL1, the glycosylation of IgG, the GlycoAge test (a glycosylation-based marker of aging) and the plasma level of inflammatory and liver damage markers. Our results show that: 1) plasmatic B4GALTs activity is a new marker of aging, showing a linear increase throughout the whole age range. 2) plasmatic ST6GAL1 was high only in children and in people above 80, showing a quadratic relationship with age. 3) Neither plasmatic glycosyltransferase correlated with markers of liver damage. 4) plasmatic ST6GAL1 showed a positive association with acute phase proteins in offspring of short lived parents, but not in centenarians or in their offspring. 5) Although the glycosylation of IgGs was not correlated with the level of the two plasmatic glycosyltransferases, it showed progressive age-associated changes consistent with a shift toward a pro-inflammatory glycotype.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Antigens, CD
- Biomarkers
- Child
- Child, Preschool
- Female
- Galactosyltransferases
- Glycosylation
- Humans
- Immunoglobulin G
- Infant
- Infant, Newborn
- Inflammation
- Liver Diseases
- Male
- Middle Aged
- Prognosis
- Sialyltransferases
- Young Adult
Keywords
- Gerotarget
- antibody glycosylation
- inflammaging
- plasma galactosyltransferases
- plasma sialyltransferases
- soluble glycosyltransferases