Activation of proteolytic enzymes and depression of the sarcolemmal Na+/K+-ATPase in ischemia–reperfused heart may be mediated through oxidative stress
Autor: | Naranjan S. Dhalla, Raja B. Singh, Darren H. Freed, Larry V. Hryshko |
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Rok vydání: | 2012 |
Předmět: |
Male
Time Factors Physiology Matrix metalloproteinase inhibitor Sodium-Potassium-Exchanging ATPase Down-Regulation Myocardial Reperfusion Injury In Vitro Techniques Matrix Metalloproteinase Inhibitors Matrix metalloproteinase medicine.disease_cause Antioxidants Ventricular Function Left Rats Sprague-Dawley Enzyme activator Sarcolemma Physiology (medical) Ventricular Pressure medicine Animals Protease Inhibitors Na+/K+-ATPase Hypoxia Pharmacology biology Calpain Chemistry Myocardium Proteolytic enzymes General Medicine Oxidants Matrix Metalloproteinases Rats Cell biology Enzyme Activation Perfusion Oxidative Stress Biochemistry Ischemic Preconditioning Myocardial biology.protein Oxidative stress |
Zdroj: | Canadian Journal of Physiology and Pharmacology. 90:249-260 |
ISSN: | 1205-7541 0008-4212 |
Popis: | We tested whether the activation of proteolytic enzymes, calpain, and matrix metalloproteinases (MMPs) during ischemia–reperfusion (I/R) is mediated through oxidative stress. For this purpose, isolated rat hearts were subjected to a 30 min global ischemia followed by a 30 min reperfusion. Cardiac function was monitored and the activities of Na+/K+-ATPase, Mg2+-ATPase, calpain, and MMP were measured. Depression of cardiac function and Na+/K+-ATPase activity in I/R hearts was associated with increased calpain and MMP activities. These alterations owing to I/R were similar to those observed in hearts perfused with hypoxic medium, H2O2 and xanthine plus xanthine oxidase. The I/R-induced changes were attenuated by ischemic preconditioning as well as by perfusing the hearts with N-acetylcysteine or mercaptopropionylglycine. Inhibition of MMP activity in hearts treated with doxycycline depressed the I/R-induced changes in cardiac function and Na+/K+-ATPase activity without affecting the calpain activation. On the other hand, inhibition of calpain activity upon treatment with leupeptin or MDL 28170 significantly reduced the MMP activity in addition to attenuating the I/R-induced alterations in cardiac function and Na+/K+-ATPase activity. These results suggest that the I/R-induced depression in Na+/K+-ATPase and cardiac function may be a consequence of the increased activities of both calpain and MMP because of oxidative stress in the heart. |
Databáze: | OpenAIRE |
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