Correlation between oxidative Stress and Alteration of Intracellular Calcium Handling in Isoproterenol-Induced Myocardial Infarction

Authors: Díaz-Muñoz, Mauricio; Álvarez-Pérez, Marco; Yáñez, Lucía; Vidrio, Susana; Martínez, Lidia; Rosas, Gisele; Yáñez, Mario; Ramírez, Sotero; Sánchez, Victoria1

Source: Molecular and Cellular Biochemistry, Volume 289, Numbers 1-2, September 2006 , pp. 125-136(12)

Publisher: Springer

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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.

Keywords: ryanodine receptor; inositol trisphosphate receptor; Ca2+-ATPases; xanthine oxidase; nitric oxide; glutathione

Document Type: Research article

DOI: 10.1007/s11010-006-9155-1

Affiliations: 1: Email: vchagoya@ifc.unam.mx

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