Calcium sensing receptor protects high glucose-induced energy metabolism disorder via blocking gp78-ubiquitin proteasome pathway

Cell Death & Disease
Yuehong WangChangqing Xu

Abstract

Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the patients with diabetes. The calcium sensing receptor (CaSR) is a G protein-coupled receptor, which is involved in maintaining calcium homeostasis, regulating cell proliferation and apoptosis, and so on. In our previous study, we found that CaSR expression, intracellular calcium levels and cardiac function were all significantly decreased in DCM rats; however, the exact mechanism are not clear yet. The present study revealed the protective role of CaSR in myocardial energy metabolism disorder induced by high glucose (HG) as well as the underlying mechanism. Here, we demonstrated that HG decreased the expression of CaSR, mitochondrial fusion proteins (Mfn1, Mfn2), cell gap junction related proteins (Cx43, β-catenin, N-cadherin), and intracellular ATP concentration. In contrast, HG increased extracellular ATP concentration, the expression of gp78, mitochondrial fission proteins (Fis1, Drp1), and the ubiquitination levels of Mfn1, Mfn2 and Cx43. Moreover, CaSR agonist and gp78-siRNA significantly reduced the above changes. Taken together, these results suggest that HG induces myocardial energy metabolism disorder via decrease of CaSR expression, and activa...Continue Reading

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Citations

Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lichan TaoFei Hua
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Namrita KaurWei Liu
Apr 4, 2021·International Journal of Molecular Sciences·Sai Sahana Sundararaman, Emiel P C van der Vorst
Jul 20, 2021·Frontiers in Medicine·Teresa SalvatoreFerdinando Carlo Sasso

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Methods Mentioned

BETA
immunocoprecipitation
ubiquitination
immunoprecipitation
Assay
transfection
Protein Assay
electrophoresis
pull-down

Software Mentioned

Image J
Bio
Rad Quantity One

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