SNX17 produces anti-arrhythmic effects by preserving functional SERCA2a protein in myocardial infarction

International Journal of Cardiology
Dandan ZhaoHongli Shan

Abstract

Sorting nexin 17 (SNX17) is a critical cytoplasmic adaptor protein that regulates endosomal trafficking of membrane proteins to determine their recycling and/or degradation. The potential role of SNX17 in cardiovascular pathophysiology has not been reported. Cardiac arrhythmias were monitored using standard limb lead II electrocardiograph, and cardiac performances were determined by echocardiography in a rat model of myocardial infarction (MI) created by left anterior descending coronary artery ligation. We found that SNX17 was substantially downregulated in ischemic myocardium. The downregulation contributed to the cardiac electrical disturbances and contractile dysfunction as SNX17 replacement mitigated the detrimental alterations of MI hearts. Specifically, silence of SNX17 expression using RNA interference caused intracellular Ca2+ overload as revealed by the abnormal rise of resting [Ca2+]i and deceleration of Ca2+ decay, whereas SNX17 overexpression using vectors elicited the opposite effects. Moreover, the protein level of SERCA2a was significantly decreased by silencing SNX17. Immunohistochemistry indicated that SNX17 and SERCA2a were co-localized, and co-immunoprecipitation revealed the binding between the phox-homolog...Continue Reading

Citations

Mar 17, 2019·Clinical Science·Jian YangChunyu Zeng
Feb 17, 2019·Journal of Molecular and Cellular Cardiology·Jae Gyun OhDongtak Jeong
May 3, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yanping ZhangDan Shi
Dec 1, 2021·The FEBS Journal·Juan HuangJian Yang

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