Leucoisoprenochrome-o-semiquinone formation in freshly isolated adult rat cardiomyocytes

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Remiao, F (Author) FFUP; Rettori, D (Author) Other; Han, D (Author) Other; Carvalho, F (Author) FFUP; Bastos, ML (Author) FFUP; Cadenas, E (Author) Other

Journal

Title: Chemical Research in Toxicology

Vol. 17

Pages: 1584-1590

ISSN: 0893-228X

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 14 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-7DZ

DOI: 10.1021/tx049924g

Abstract (EN): Sustained high levels of circulating catecholamines can lead to cardiotoxicity. There is increasing evidence that this process may result from metal-catalyzed catecholamine oxidation into semiquinones, quinones, and aminochromes. We have previously shown that Cu2+-induced oxidation of isoproterenol into isoprenochrome induces toxic effects in isolated cardiomyocytes. The aim of this study was to characterize the isoproterenol oxidation process and to locate the formation of semiquinone radicals in cardiomyocyte suspensions. Freshly isolated rat cardiomyocytes were incubated with 1 or 10 mM isoproterenol and 20 mu M Cu2+ for 4 h. The formation of an isoproterenol oxidation radical was detected in the extracellular medium, cells, membranes, and heavy organelles by electron spin resonance spectroscopy. An electron spin resonance signal assigned to leucoisoprenochrome-o-semiquinone increased in a time-dependent manner in the extracellular medium. A second electron spin resonance signal, characteristic of an immobilized radical, was also found in the cardiomyocytes. The latter was attributed to leucolsoprenochrome-o-semiquinone immobilized on cellular components such as membranes, cytoskeleton, nucleus, and heavy organelles. In addition, the levels of leucoisoprenochrome-o-semiquinone decreased in the presence of glutathione. Computer simulations of the experimental spectra indicate the formation of two distinct isomeric leucoisoprenochrome-o-semiquinone radicals during isoproterenol oxidation. The present study shows that the isoproterenol oxidation in isolated rat cardiomyocytes correlates with the formation of leucoisoprenochrome-o-semiquinone in the cells and in the extracellular medium, suggesting that it might be involved in cardiotoxicity induced by the oxidation of catecholamines.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7