Altered Glycosylation in the Aging Heart.
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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: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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