Dysregulation of the calcium handling protein, CCDC47, is associated with diabetic cardiomyopathy

Cell & Bioscience
Khampaseuth ThapaRangaprasad Sarangarajan

Abstract

Diabetes mellitus is associated with an increased risk in diabetic cardiomyopathy (DCM) that is distinctly not attributed to co-morbidities with other vasculature diseases. To date, while dysregulation of calcium handling is a key hallmark in cardiomyopathy, studies have been inconsistent in the types of alterations involved. In this study human cardiomyocytes were exposed to an environmental nutritional perturbation of high glucose, fatty acids, and l-carnitine to model DCM and iTRAQ-coupled LC-MS/MS proteomic analysis was used to capture proteins affected by the perturbation. The proteins captured were then compared to proteins currently annotated in the cardiovascular disease (CVD) gene ontology (GO) database to identify proteins not previously described as being related to CVD. Subsequently, GO analysis for calcium regulating proteins and endoplasmic/sarcoplasmic reticulum (ER/SR) associated proteins was carried out. Here, we identified CCDC47 (calumin) as a unique calcium regulating protein altered in our in vitro nutritional perturbation model. The cellular and functional role of CCDC47 was then assessed in rat cardiomyocytes. In rat H9C2 myocytes, overexpression of CCDC47 resulted in increase in ionomycin-induced calcium...Continue Reading

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Citations

Aug 22, 2020·ELife·Philip T McGilvrayRobert J Keenan

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Methods Mentioned

BETA
flow cytometry
PCR
glycosylation
deamidation
fluorescence microscopy
Transfection

Software Mentioned

excel
Mascot
Image J
Proteome Discoverer
GraphPad Prism
Xcalibur

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