title: Correlation between oxidative stress and alteration of intracellular calcium handling in isoproterenol-induced myocardial infarction.
abstract: Myocardial Ca(2+) 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 Ca(2+) homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca(2+) content, the activity of Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla-Querétaro, México, México.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Díaz-Muñoz
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Alvarez-Pérez
authors.forename: Lucía
authors.initials: L
authors.lastname: Yáñez
authors.forename: Susana
authors.initials: S
authors.lastname: Vidrio
authors.forename: Lidia
authors.initials: L
authors.lastname: Martínez
authors.forename: Gisele
authors.initials: G
authors.lastname: Rosas
authors.forename: Mario
authors.initials: M
authors.lastname: Yáñez
authors.forename: Sotero
authors.initials: S
authors.lastname: Ramírez
authors.forename: Victoria Chagoya
authors.initials: VC
authors.lastname: de Sánchez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D007545:Isoproterenol; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009203:Myocardial Infarction / Q000139:chemically induced*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D005978:Glutathione; D007545:Isoproterenol