Abstract
Myocardial Ca2+ overload and oxidative stress are well documented effects associated to isoproterenol (ISO)-induced myocardial necrosis, but information correlating these two issues is scarce. Using an ISO-induced myocardial infarction model, 3 stages of myocardial damage were defined: pre-infarction (0–12 h), infarction (12–24 h) and post-infarction (24–96 h). Alterations in Ca2+ homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca2+ content, the activity of Ca2+ handling proteins, and by quantifying TBARs, nitric oxide (NO) and oxidative protein damage (changes in carbonyl and thiol groups). Free radicals generated system, antioxidant enzymes and oxidative stress (GSH/GSSG ratio) were also monitored at different times of ISO-induced cardiotoxicity. The Ca2+ overload induced by ISO was counterbalanced by a diminution in the ryanodine receptor activity and the Na+-Ca+2 exchanger as well as by the increase in both calcium ATPases activities (vanadate- and thapsigargine-sensitive) and mitochondrial Ca2+ uptake during pre-infarction and infarction stages. Pro-oxidative reactions and antioxidant defences during the 3 stages of cardiotoxicity were observed, with maximal oxidative stress during the infarction. Significant correlations were found among pro-oxidative reactions with plasmalemma and sarcoplasmic reticulum Ca2+ ATPases, and ryanodine receptor activities at the onset and development of ISO-induced infarction. These findings could be helpful in the design of antioxidant therapies in this pathology.
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Díaz-Muñoz, M., Álvarez-Pérez, M.A., Yáñez, L. et al. Correlation between oxidative Stress and Alteration of Intracellular Calcium Handling in Isoproterenol-Induced Myocardial Infarction. Mol Cell Biochem 289, 125–136 (2006). https://doi.org/10.1007/s11010-006-9155-1
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DOI: https://doi.org/10.1007/s11010-006-9155-1