Cu2+-induced isoproterenol oxidation into isoprenochrome in adult rat calcium-tolerant cardiomyocytes

• Type: Article in International Scientific Journal
• Date: 2002

Authors

Remiao, F (Author) FFUP; Carvalho, M (Author) Other; Carmo, H (Author) FFUP; Carvalho, F (Author) FFUP; Bastos, ML (Author) FFUP

Journal

Title: Chemical Research in Toxicology

Vol. 15

Pages: 861-869

ISSN: 0893-228X

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 41 Citations

Scopus - 49 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-P3R

DOI: 10.1021/tx025518q

Abstract (EN): Sustained high levels of circulating catecholamines may induce cardiotoxicity. There is increasing evidence that this could result from catecholamine oxidation into aminochromes, which is catalyzed by transition metals. In fact, it has already been shown that copper-induced oxidation of the beta-agonist isoproterenol decreases the viability of isolated cardiomyocytes. Thus, the aim of this work was to contribute for the clarification of the mechanisms underlying the toxic effects of isoproterenol, Cu2+ and their concomitant effect in isolated rat cardiomyocytes. Freshly isolated calcium-tolerant cardiomyocytes from adult rat were incubated with 1 mM isoproterenol, 20 muM Cu2+ or with both during 4 h. Isoproterenol and its aminochrome (isoprenochrome), and reduced and oxidized glutathione were measured at each hour in the incubation medium and in the cells. The intracellular activities of the selenium-dependent glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were determined after 4 h of incubation. Isoprenochrome was found in both cells and incubation medium in samples incubated with isoproterenol alone. However, in the isoproterenol plus Cu2+ samples, a greater depletion of isoproterenol accompanied by a proportional increase of isoprenochrome was observed. This higher ISO oxidation resulted in the depletion of intracellular glutathione and in the release of oxidized glutathione to the incubation medium. The content of total glutathione (intra- and extracellular) and the intracellular activity of the selenium-dependent glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were also decreased in the isoproterenol plus Cu2+ samples. These results seem to indicate that the oxidative stress resulting from catecholamine/transition metal association may contribute to catecholamine cardiotoxicity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9