Acetaminophen attenuates peroxynitrite-activated matrix metalloproteinase-2-mediated troponin I cleavage in the isolated guinea pig myocardium

Journal of Molecular and Cellular Cardiology
Tyler H RorkG F Merrill

Abstract

The peroxynitrite-mediated activation of matrix metalloproteinase-2 (MMP-2) and subsequent cleavage of troponin I (TnI) in ventricular myocytes is a detrimental effect of ischemia/reperfusion injury. We hypothesized that acetaminophen, an effective antioxidant against peroxynitrite, would attenuate activation of MMP-2 and improve cardiac mechanical function. Isolated, perfused guinea pig hearts (Langendorff) were treated with either acetaminophen [0.35 mmol/l] or its vehicle and administered a bolus injection of peroxynitrite (6 microM) after reaching steady state function. Hemodynamic, metabolic, and mechanical effects were recorded, and coronary effluent concentrates or supernatant from heart homogenates were subjected to Western blotting and gelatin zymography. Hemodynamic and metabolic data showed no difference between acetaminophen- and vehicle-treated hearts. Mechanical data revealed that treatment with acetaminophen preserved contractile function (particularly diastolic function) after peroxynitrite administration. For example, 5 min after administration of peroxynitrite percent baseline -dP/dt(max) was 10+/-3% and -4+/-7% (P<0.05) in acetaminophen- and vehicle-treated hearts, respectively. Western blotting and gel zymog...Continue Reading

Citations

Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
Apr 15, 2009·Journal of Cardiovascular Pharmacology·Diego Romero-PerezFrancisco Villarreal
Jun 28, 2008·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·W Stephen WaringJanice M Pettie
Sep 4, 2009·The Journal of Surgical Research·Shu-Juan LiJian-Shi Lou
Apr 25, 2008·Free Radical Biology & Medicine·Mark J KohrMark T Ziolo
Feb 2, 2008·Biochemical Pharmacology·Howard G ShertzerMary Beth Genter
Nov 3, 2009·Experimental Physiology·Martín DonatoRicardo J Gelpi
Feb 19, 2008·American Journal of Obstetrics and Gynecology·Chien OhLoren P Thompson
Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi
Oct 9, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Norell M HadzimichalisGary F Merrill
Mar 14, 2014·Molecular and Cellular Biochemistry·Bruno BuchholzRicardo J Gelpi
Mar 21, 2017·Molecular and Cellular Biochemistry·Martín DonatoRicardo J Gelpi
Aug 16, 2008·Experimental Biology and Medicine·Kathryn M Jaques-RobinsonGary F Merrill

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