Altered Glycosylation in the Aging Heart.
Ontology highlight
ABSTRACT:
SUBMITTER: Franzka P
PROVIDER: S-EPMC8194361 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Heart failure is one of the leading causes of death in an ageing population. Hallmarks are cardiac hypertrophy, fibrosis and inflammation. The molecular mechanisms, however, are poorly understood. Glycosylation is one of the most common posttranslational modifications of proteins, which can have important consequences for protein folding, function and turnover. We hypothesized that changes in glycoprotein abundance and glycosylation patterns may contribute to cardiac aging. Western Blot analysis suggests increased protein mannosylation in the aging heart. Glycoprotein pull-downs from heart lysates of young (3 months) and old (2 years) mice in combination with quantitative mass spectrometry support widespread alterations of the glycoproteome in aged hearts.
2021-05-12 | PXD023740 | Pride
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Project description:Prolactin is a peptide hormone produced in the anterior pituitary, which increase in several physiological and pathological situations. It is unclear if hyperprolactinaemia may affect glycosylation of immunoglobulin G (IgG). Twenty-five patients with hyperprolactinemia and 22 healthy control subjects were included in the study. The groups had similar age and gender distribution. A panel of hormonal and haematological analyses, creatinine, glucose, liver enzymes and immunoglobulins were measured by routine clinical methods. IgG was purified from serum by Protein G Sepharose. Sialic acid was released from IgG by use of neuraminidase followed by quantification on high performance anion-exchange chromatography with pulsed amperometric detection. Tryptic glycopeptides of IgG was analysed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Hormone and immunoglobulin levels were similar in the two groups, except for IgA and prolactin. Significantly higher IgG1 and IgG2/3 galactosylation was found in the patient group with hyperprolactinaemia compared to controls. (A significant correlation between prolactin and IgG2/3 galactosylation (Rs 0.61, p<0.001) was found for samples with prolactin values below 2000 mIU/L. The relative amount of sialylated and bisecting glycans on IgG did not differ between patients and controls. The four macroprolactinaemic patients showed decreased relative amount of bisecting IgG2/3 glycans. Hyperprolactinaemia was found to be associated with increased galactosylation of IgG1and IgG2/3. This may have impact on IgG interactions with Fc-receptors, complement and lectins, and consequently lead to an altered immune response.
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Project description:The molecular mechanisms of schizophrenia have been under investigation for decades; however, the exact causes of this debilitating neuropsychiatric disorder are still unknown. Previous studies have identified multiple affected neurotransmitter systems, brain regions, and cell types, each making a unique contribution to symptom presentation and pathophysiology. Numerous studies have identified gene and protein expression changes in schizophrenia, but the role of post-translational modifications, specifically N-glycosylation, has only recently become a target of investigation. N-glycosylation of molecules associated with glutamatergic neurotransmission is disrupted in schizophrenia, but it was unknown if these alterations are exclusive to the glutamatergic system or due to a more generalized deficit.In normal human cortex, we found evidence for N-glycosylation of the ?1, ?1, and ?2 ?-aminobutyric type A receptor (GABAAR) subunits using deglycosylation protein shift assays. This was confirmed with lectin affinity assays that revealed glycan attachment on the ?1, ?4, and ?1-3 GABAAR subunits. Examining GABAAR subunit N-glycosylation in matched pairs of schizophrenia (N=14) and comparison (N=14) of superior temporal gyrus revealed a smaller molecular mass of immature N-glycans on the ?1 subunit, more immature N-glycosylation of the 49-kDa ?1 subunit isoform, and altered total N-glycosylation of the ?2 GABAAR subunit in schizophrenia. Measures of altered N-glycosylation of the ?1 and ?2 subunits were confounded by an increased apparent molecular mass of all ?1 and ?2 subunit isoforms in schizophrenia. Although N-glycosylation of ?1, ?1, and ?2 were all changed in schizophrenia, the concentrations of GABAAR subunits themselves were unchanged. These findings suggest that disruptions of N-glycosylation in schizophrenia are not exclusive to glutamate and may indicate a potential disruption of a central cell signaling process in this disorder.
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