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Roles of Transient Receptor Potential Channel 6 in Glucose-induced Cardiomyocyte Injury

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Specialty Endocrinology
Date 2022 May 18
PMID 35582666
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Abstract

Background: Diabetic cardiomyopathy (DCM) is a serious complication of end-stage diabetes that presents symptoms such as cardiac hypertrophy and heart failure. The transient receptor potential channel 6 (TRPC6) protein is a very important selective calcium channel that is closely related to the development of various cardiomyopathies.

Aim: To explore whether TRPC6 affects cardiomyocyte apoptosis and proliferation inhibition in DCM.

Methods: We compared cardiac function and myocardial pathological changes in wild-type mice and mice injected with streptozotocin (STZ), in addition to comparing the expression of TRPC6 and P-calmodulin-dependent protein kinase II (P-CaMKII) in them. At the same time, we treated H9C2 cardiomyocytes with high glucose and then evaluated the effects of addition of SAR, a TRPC6 inhibitor, and KN-93, a CaMKII inhibitor, to such H9C2 cells in a high-glucose environment.

Results: We found that STZ-treated mice had DCM, decreased cardiac function, necrotic cardiomyocytes, and limited proliferation. Western blot and immunofluorescence were used to detect the expression levels of various appropriate proteins in the myocardial tissue of mice and H9C2 cells. Compared to those in the control group, the expression levels of the apoptosis-related proteins cleaved caspase 3 and Bax were significantly higher in the experimental group, while the expression of the proliferation-related proteins proliferating cell nuclear antigen (PCNA) and CyclinD1 was significantly lower. and , the expression of TRPC6 and P-CaMKII increased in a high-glucose environment. However, addition of inhibitors to H9C2 cells in a high-glucose environment resulted in alleviation of both apoptosis and proliferation inhibition.

Conclusion: The inhibition of apoptosis and proliferation of cardiomyocytes in a high-glucose environment may be closely related to activation of the TRPC6/P-CaMKII pathway.

Citing Articles

Differential changes in cyclic adenosine 3'-5' monophosphate (cAMP) effectors and major Ca handling proteins during diabetic cardiomyopathy.

Chaoul V, Hanna R, Hachem P, El Hayek M, Nour-Eldine W, Abou-Khalil P J Cell Mol Med. 2023; 27(9):1277-1289.

PMID: 36967707 PMC: 10148055. DOI: 10.1111/jcmm.17733.

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