Infection with AV-SUR2A protects H9C2 cells against metabolic stress: a mechanism of SUR2A-mediated cytoprotection independent from the K(ATP) channel activity.

Biochimica Et Biophysica Acta
Qingyou DuA Jovanović

Abstract

Transgenic mice overexpressing SUR2A, a subunit of ATP-sensitive K(+) (K(ATP)) channels, acquire resistance to myocardial ischaemia. However, the mechanism of SUR2A-mediated cytoprotection is yet to be fully understood. Adenoviral SUR2A construct (AV-SUR2A) increased SUR2A expression, number of K(ATP) channels and subsarcolemmal ATP in glycolysis-sensitive manner in H9C2 cells. It also increased K(+) current in response to chemical hypoxia, partially preserved subsarcolemmal ATP and increased cell survival. Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K(+) conductance, abolished the effect of SUR2A on K(+) current, did not affect SUR2A-induced increase in subsarcolemmal ATP and partially inhibited SUR2A-mediated cytoprotection. Infection with 193gly-M-LDH, an inactive mutant of muscle lactate dehydrogenase, abolished the effect of SUR2A on K(+) current, subsarcolemmal ATP and cell survival; the effect of 193gly-M-LDH on cell survival was significantly more pronounced than those of Kir6.2AFA. We conclude that AV-SUR2A increases resistance to metabolic stress in H9C2 cells by increasing the number of sarcolemmal K(ATP) channels and subsarcolemmal ATP.

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Citations

Sep 18, 2010·Human Reproduction·Qingyou DuAleksandar Jovanović
Feb 2, 2013·Mechanisms of Ageing and Development·Qingyou DuAleksandar Jovanović
Apr 5, 2016·International Journal of Molecular Sciences·Yung-Ming ChangChih-Yang Huang
Mar 14, 2013·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Faisel KhanAleksandar Jovanović
Oct 23, 2012·The International Journal of Biochemistry & Cell Biology·Thomas BallantyneAleksandar Jovanović
Dec 7, 2010·Journal of Molecular and Cellular Cardiology·Christin C T ChaoHerbert Y Gaisano
Jan 26, 2017·Journal of Cellular and Molecular Medicine·Khaja Shameem Mohammed AbdulAleksandar Jovanović
Aug 25, 2010·Journal of Cellular and Molecular Medicine·Andriy SukhodubAleksandar Jovanović
Jun 28, 2019·The Journal of Antibiotics·Sharabh SinhaAleksandar Jovanović
May 28, 2020·Pflügers Archiv : European journal of physiology·Rajni SudhirAleksandar Jovanović

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Methods Mentioned

BETA
PCR
Assay
FCS
transgenic

Software Mentioned

Quantiscan
pClamp8
iCycler [UNK] Real - Time Detection System
SigmaStat

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