Altered Glycosylation in the Aging Heart

Franzka, Patricia; Krüger, Lynn; Schurig, Mona K; Olecka, Maja; Hoffmann, Steve; Blanchard, Véronique; Hübner, Christian A.

doi:10.3389/fmolb.2021.673044

Cited by 17 publications

(16 citation statements)

References 63 publications

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“…High levels of core fucosylation were maintained in healthy NC‐rich NP tissue during maturation which was an unexpected finding considering that core fucosylation is arguably affected with aging 38,39 . Core fucosylation is involved in conditions such as cancer, 40–42 cardiac regenerative capacity, 43 liver disease, 44 and autoimmune diseases, 45 potentially through disruption of cell recognition, signaling, and adhesion 46,47 .…”

Section: Discussionmentioning

confidence: 93%

An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation

et al. 2023

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Degeneration of the intervertebral disc is an age‐related condition. It also accompanies the disappearance of the notochordal cells, which are remnants of the developmental stages of the nucleus pulposus (NP). Molecular changes such as extracellular matrix catabolism, cellular phenotype, and glycosaminoglycan loss in the NP have been extensively studied. However, as one of the most significant co‐ and posttranslational modifications, glycosylation has been overlooked in cells in degeneration. Here, we aim to characterize the N‐glycome of young and mature NP and identify patterns related to aging. Accordingly, we isolated N‐glycans from notochordal cell‐rich NP from porcine discs, characterized them using a combined approach of exoglycosidase digestions and analysis with hydrophilic interaction ultra‐performance liquid chromatography and mass spectrometry. We have assigned over 300 individual N‐glycans for each age group. Moreover, we observed a notable abundance of antennary structures, galactosylation, fucosylation, and sialylation in both age groups. In addition, as indicated from our results, increasing outer arm fucosylation and decreasing α(2,3)‐linked sialylation with aging suggest that these traits are age‐dependent. Lastly, we have focused on an extensive characterization of the N‐glycome of the notochordal cell‐rich NP in aging without inferred degeneration, describing glycosylation changes specific for aging only. Our findings in combination with those of other studies, suggest that the degeneration of the NP does not involve identical processes as aging.

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Section: Discussionmentioning

confidence: 93%

An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation

et al. 2023

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“…We recently showed that hyperglycosylation of proteins is correlated with increased plasma mannose levels ( 2 ). Moreover, we showed that increased GMPPB levels correlate with protein hypermannosylation and enhanced plasma mannose levels ( 24 ). Altered glycosylation may affect protein stability and conformation, protein interactions and adhesion, as well as protein activity and localization ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Membranes were blocked in 2% BSA for 1 h at RT and incubated with primary antibodies at appropriate dilutions in tris-buffered saline supplemented with 0.1% Tween-20 (TBS-T) overnight at 4°C. The following primary antibodies were used: rabbit anti-GMPPA (#15517-1-AP, Proteintech, Rosemont, IL, USA) 1:500, rabbit anti-GMPPB (#15094-1-AP, Proteintech, Rosemont, IL, USA) 1:500, rabbit anti-GAPDH (#10494-1-AP, Proteintech, Rosemont, IL, USA) 1:1,000, self-made mouse anti-oligomannose antibody (6–9 terminal mannose residues) 1:50 [gift of Rüdiger Horstkorte, Halle ( 24 )]. Membranes were washed in TBS-T and primary antibodies were detected with horseradish peroxidase-conjugated secondary antibodies in an appropriate dilution.…”

Section: Methodsmentioning

confidence: 99%

Altered mannose metabolism in chronic stress and depression is rapidly reversed by vitamin B12

et al. 2022

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GDP-Mannose Pyrophosphorylase B (GMPPB) is a key enzyme for glycosylation. Previous studies suggested a dysregulation of GMPBB and mannose in depression. Evidence, however, was sporadic and interventions to reverse these changes are unknown. Here, we show that GMPPB protein, but not RNA abundance is increased in the postmortem prefrontal cortex (PFC) of depressed patients and the chronic variable stress (CVS) mouse-model. This is accompanied by higher plasma mannose levels. Importantly, a single dose of intraperitoneally administered vitamin B12, which has previously been shown to rapidly reverse behavioral symptoms and molecular signatures of chronic stress in mice, normalized GMPPB plasma mannose levels and elevated GDP-mannose abundance. In summary, these data underline metabolic dysregulation in chronic stress and depression and provide further support for rapid effects of vitamin B12 on chronic stress.

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“…Changes in the glycoproteome probably contribute to the age -related functional decline of the cardiovascular system as well as the heart and the aorta performance. 43, 44 Glycans covering the surface of EVs form a corona that has been recognized as a crucial mediator of EV functions. 45,46 Glycomic profile of melanoma--derived ectosomes showed important correlation with melanoma malignancy.…”

Section: What Do Extracellular Vesicles Contain?mentioning

confidence: 99%

Extracellular vesicles in vascular pathophysiology: beyond their molecular content

Stępień¹,

Durak-Kozica²,

Moskal³

2023

Polish Archives of Internal Medicine

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Extracellular vesicles in vascular pathophysiology 1 Currently, the topic of extracellular vesicles (EVs) and their involvement in disease promotion and progression is gaining important insight in diagnostics and treatment. 5 In this review, we focus on specific EV characteristics, still not intensively investigated, which contribute to the biological activity of EVs, that is, composition of the EV surface called a corona, and its charge.The biological activity of EVs depends on their cargo and their biological availability and biostability. The estimated blood plasma concentration of EVs in healthy individuals is between 10 8 and 10 14 EVs/ml. Such discrepancies, more than 6 orders of magnitude, depend mainly on the isolation protocol and possible contamination by other colloidal particles present in the plasma, such as lipoproteins and large protein aggregates. 6 In total platelet poor plasma, the average platelet microvesicle (PMV) content has been estimated at 10 9 to 10 10 EVs/ml in patients on antiplatelet drugs and healthy individuals. PMV abundance depends mainly on the plasma purity and preanalytical handling. 7-11 Assuming that one -third of the plasma EVs is of platelet origin, the number of the plasma EVs can be approximately 10 10 EVs/ml. 6 The average plasma residence time of intravenously delivered EVs ranges from 30 to 80 minutes and it is mainly regulated by the phagocyting activity of the mononuclear phagocyte system and by Introduction When about 50 years ago Wolf 1 noticed that some tiny and highly abundant objects present in human blood plasma contribute to clotting events, it seemed that there is something beyond clotting factors that may support platelets / thrombocytes in their aggregation and formation of a thrombus. This coagulant particulate material released from platelets (referred to as "platelet dust") was produced in considerably larger amounts than required for thrombin generation. It was detected not only in plasma but also in serum, and its presence seemed to be associated with the platelet -like activity of the serum. 1 The platelet activation leads to secretion of granules containing the procoagulant material and proteins involved in cytoskeletal arrangement, synaptic transportation, and secretion from their internal space. 2 The processes of the formation and secretion of platelet "particles" are analogous to the processes occurring in other cells, including endothelial cells. They result in the formation of 2 types of membrane vesicles: bigger ones shed from the surface and named microvesicles (ectosomes) of 100 nm to 1 µm in diameter, and exosomes, measuring 40 nm to 100 nm in diameter. The latter are similar in size to the internal vesicles in multivesicular bodies (MVBs) and α -granules, 3,4 and can be compared to endothelial vesiculation (FIguRE 1).

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Altered Glycosylation in the Aging Heart

Cited by 17 publications

References 63 publications

An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation

An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation

Altered mannose metabolism in chronic stress and depression is rapidly reversed by vitamin B12

Extracellular vesicles in vascular pathophysiology: beyond their molecular content

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