CSQ2 glycosylation did not affect SOICR nor polymerisation in HEK293 cells or in diabetic and heart failure animal models, showing no disease-related changes.
CSQ2 glycosylation does not appear to influence SOICR in HEK293 cells and is not altered in the studied rat and sheep models of diabetes and heart failure.
Absolute Event Rate: 0% vs 0%
The contraction of the heart relies on the controlled release of calcium ions (Ca²⁺) from the sarcoplasmic reticulum (SR) via ryanodine receptor 2 (RyR2). In cardiac dysfunction, such as heart failure (HF), RyR2 may become predisposed to store overload induced Ca²⁺ release (SOICR), reducing Ca²⁺ available for physiological release and contributing to weaker contractions. Diabetes mellitus (DM) increases the risk of HF progression and is associated with a higher incidence of SOICR. Calsequestrin-2 (CSQ2), the primary Ca²⁺ buffer within the SR, mitigates SOICR through Ca²⁺-induced polymerisation. As a glycoprotein with an N-glycan at N335, CSQ2’s glycosylation is hypothesised to enhance polymerisation and improve buffering capacity. Aberrant glycosylation, in contrast, may impair polymerisation and exacerbate SOICR. Dysregulated CSQ2 glycosylation has been observed in canine HF models, implicating it in HF pathology, yet its physiological consequences remain unclear. This study aimed to determine the effect of CSQ2 glycosylation on RyR2 associated SOICR. Ca²⁺ imaging in HEK293 cells expressing RyR2 and CSQ2 was used to assess SOICR, while SDS-PAGE and native PAGE immunoblots were performed to evaluate CSQ2 glycosylation and polymerisation. Hyperglycaemic conditions did not alter CSQ2 glycosylation, polymerisation, or SOICR in HEK293 cells. Similarly, experiments with double-glycosylated (CSQ2-K206N) and non-glycosylated (CSQ2-KK) mutants revealed no changes in SOICR relative to wild-type CSQ2 in HEK293 cells, despite significant differences in glycosylation. Following this, CSQ2 glycosylation and polymerisation were investigated in DM rats and HF sheep models. Neither model exhibited changes in CSQ2 glycosylation or polymerisation in diseased animals compared to controls. In all models, a novel population of CSQ2 present as a monomer with no observable glycosylation was observed. These findings suggest that CSQ2 glycosylation may not influence SOICR in HEK293 cells and is not altered in the studied models of DM and HF. Further research is required to clarify the role of CSQ2 glycosylation in SOICR and its potential contributions to cardiac disease.
Elliot Tobias Sibbles (Tue,) reported a other. CSQ2 glycosylation did not affect SOICR nor polymerisation in HEK293 cells or in diabetic and heart failure animal models, showing no disease-related changes.
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