Ischemia/reperfusion-induced myosin light chain 1 phosphorylation increases its degradation by matrix metalloproteinase 2.

The FEBS Journal
Virgilio J J CadeteG Sawicki

Abstract

Degradation of myosin light chain 1 (MLC1) by matrix metalloproteinase 2 (MMP-2) during myocardial ischemia/reperfusion (I/R) has been demonstrated. However, the exact mechanisms controlling this process remain unknown. I/R increases the phosphorylation of MLC1, but the consequences of this modification are not known. We hypothesized that phosphorylation of MLC1 plays an important role in its degradation by MMP-2. To examine this, isolated perfused rat hearts were subjected to 20 min global ischemia followed by 30 min of aerobic reperfusion. I/R increased phosphorylation of MLC1 (as measured by mass spectrometry). When hearts were subjected to I/R in the presence of ML-7 (a myosin light-chain kinase inhibitor) or doxycycline (an MMP inhibitor), improved recovery of contractile function was observed compared to aerobic controls, and MLC1 was protected from degradation. Enzyme kinetic studies revealed an increased affinity of MMP-2 for the phosphorylated form of MLC1 compared to non-phosphorylated MLC1. We conclude that MLC1 phosphorylation is an important mechanism controlling the intracellular action of MMP-2 and promoting degradation of MLC1. These results further support previous findings implicating post-translational modifi...Continue Reading

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Citations

Jul 6, 2014·Basic Research in Cardiology·Bryan G Hughes, Richard Schulz
Sep 28, 2014·Journal of Molecular and Cellular Cardiology·Ashley DeCouxRichard Schulz
Jun 19, 2013·The Canadian Journal of Cardiology·Virgilio J J CadeteGrzegorz Sawicki
Oct 9, 2014·Frontiers in Physiology·Katarzyna KazmierczakDanuta Szczesna-Cordary
Mar 1, 2013·American Journal of Physiology. Cell Physiology·Mokarram HossainLixin Liu
Feb 8, 2019·Journal of Cellular and Molecular Medicine·Anna Krzywonos-ZawadzkaIwona Bil-Lula
Apr 24, 2020·Cardiology Research and Practice·Anna Krzywonos-ZawadzkaIwona Bil-Lula
Oct 31, 2020·Oxidative Medicine and Cellular Longevity·Agnieszka OlejnikIwona Bil-Lula
Nov 14, 2020·International Journal of Molecular Sciences·Marta BanaszkiewiczIwona Bil-Lula
Aug 6, 2021·Canadian Journal of Kidney Health and Disease·Erick D McNairAbass Khani-Hanjani

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