A Dual Mechanism of Cytoprotection Afforded by M-LDH in Embryonic Heart H9C2 Cells

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2009 May 2

PMID 19406174

Citations 15

Authors

Sofija Jovanovic

Qingyou Du

Andriy Sukhodub

Aleksandar Jovanovic

Affiliations

Soon will be listed here.

Abstract

Muscle form of lactate dehydrogenase (M-LDH), a minor LDH form in cardiomyocytes, physically interacts with ATP-sensitive K+ (K ATP) channel-forming subunits. Here, we have shown that expression of 193gly-M-LDH, an inactive mutant of M-LDH, inhibit regulation of the K ATP channels activity by LDH substrates in embryonic rat heart H9C2 cells. In cells expressing 193gly-M-LDH chemical hypoxia has failed to activate K ATP channels. The similar results were obtained in H9C2 cells expressing Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K+ conductance. Kir6.2AFA has slightly, but significantly, reduced cellular survival under chemical hypoxia while the deleterious effect of 193gly-M-LDH was significantly more pronounced. The levels of total and subsarcolemmal ATP in H9C2 cells were not affected by Kir6.2AFA, but the expression of 193gly-M-LDH led to lower levels of subsarcolemmal ATP during chemical hypoxia. We conclude that M-LDH regulates both the channel activity and the levels of subsarcolemmal ATP and that both mechanism contribute to the M-LDH-mediated cytoprotection.

Citing Articles

SUR2A as a base for cardioprotective therapeutic strategies.

Mahdi H, Jovanovic A Mol Biol Rep. 2022; 49(7):6717-6723.

PMID: 35301655 DOI: 10.1007/s11033-022-07281-9.

Increase in cardioprotective SUR2A does not alter heart rate and heart rate regulation by physical activity and diurnal rhythm.

Sudhir R, Jaafar N, Du Q, Sukhodub A, Jovanovic S, Kreouzi M J Basic Clin Physiol Pharmacol. 2021; 33(5):619-624.

PMID: 34870381 PMC: 9508677. DOI: 10.1515/jbcpp-2021-0289.

Isosteviol prevents the development of isoprenaline‑induced myocardial hypertrophy.

Chen Y, Beng H, Su H, Han F, Fan Z, Lv N Int J Mol Med. 2019; 44(5):1932-1942.

PMID: 31545484 PMC: 6777692. DOI: 10.3892/ijmm.2019.4342.

Pyrazinamide may possess cardioprotective properties.

Sinha S, Du Q, Jovanovic S, Sukhodub A, Jovanovic A J Antibiot (Tokyo). 2019; 72(9):714-717.

PMID: 31243346 PMC: 6760625. DOI: 10.1038/s41429-019-0202-z.

Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy.

Du Q, Jovanovic S, Sukhodub A, Ngoi Y, Lal A, Zheleva M Biochem Biophys Rep. 2018; 16:12-18.

PMID: 30211323 PMC: 6132176. DOI: 10.1016/j.bbrep.2018.08.005.

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