Sep 12, 2019

Junctophilin-2 is a target of matrix metalloproteinase-2 in myocardial ischemia-reperfusion injury

Basic Research in Cardiology
Brandon Y H ChanRichard Schulz

Abstract

Junctophilin-2 is a structural membrane protein that tethers T-tubules to the sarcoplasmic reticulum to allow for coordinated calcium-induced calcium release in cardiomyocytes. Defective excitation-contraction coupling in myocardial ischemia-reperfusion (IR) injury is associated with junctophilin-2 proteolysis. However, it remains unclear whether preventing junctophilin-2 proteolysis improves the recovery of cardiac contractile dysfunction in IR injury. Matrix metalloproteinase-2 (MMP-2) is a zinc and calcium-dependent protease that is activated by oxidative stress in myocardial IR injury and cleaves both intracellular and extracellular substrates. To determine whether junctophilin-2 is targeted by MMP-2, isolated rat hearts were perfused in working mode aerobically or subjected to IR injury with the selective MMP inhibitor ARP-100. IR injury impaired the recovery of cardiac contractile function which was associated with increased degradation of junctophilin-2 and damaged cardiac dyads. In IR hearts, ARP-100 improved the recovery of cardiac contractile function, attenuated junctophilin-2 proteolysis, and prevented ultrastructural damage to the dyad. MMP-2 was co-localized with junctophilin-2 in aerobic and IR hearts by immunopr...Continue Reading

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Mentioned in this Paper

Transverse Tubule of Muscle Cell
Immunohistochemistry
Calcium-dependent protease I
Extracellular
Membrane
Calcium
Cleaved
Excitation Contraction Coupling
Matrix Metalloproteinase 2
Myocardium