Effect of aging on the circadian patterns of antioxidant enzymes in heart

ALTAMIRANO, FERNANDO GABRIEL; FERRAMOLA, MARIANA LUCILA; CASTRO PASCUAL, IVANNA CARLA; ANZULOVICH, ANA CECILIA; LACOSTE, MARÍA GABRIELA

Estancia Grande, San Luis

Congreso; XXXII Reunión Anual de la Sociedad de Biología de Cuyo; 2014

Sociedad de Biología de Cuyo

Age is a critical component of the cardiovascular disease etiology, and oxidative stress is a key element responsible for the development of age-related pathologies. This study aimed to find out whether endogenous rhythms of catalase (CAT) and glutathione peroxidase (GPx) expression and activity, as well as Nrf2 expression and GSH levels are modified in the heart of aged rat. Holtzman rats from young (3-months old) and aged (22-months old) groups were maintained under 12h-dark:12h-dark (constant darkness) conditions, during 15 days before the experiment. Nrf2, CAT and GPx mRNA expression and enzymatic activity were determined by RT-PCR and kinetic assays, respectively, in heart isolated every 4 h during a 24h period. GSH levels were measured by colorimetric assay. Temporal patterns were analyzed by the Chronos-fit software. We observed Nrf2, CAT and GPx expression vary significantly in a 24h period under constant darkness conditions (from Chronos-fit: p=0,044, p=0.013, p=0.0047, respectively), with maximal mRNA levels occurring at circadian time (CT) 13:55±00:60, 12:07±00:24, and 12:40±00:00, respectively in the heart of young rats. As expected, circadian rhythms of CAT and GPx enzymatic activity were also observed in this tissue (from Chronos-fit: p=0.0012 and p=0.036, respectively) with their rhythm´s acrophases at CT 16:21±00:50, and 21:26±00:36, respectively. We also observed temporal variation of GSH levels (p=0.0042) being maximal at CT 12:19±00:20. Interestingly, aging abolishes the oscillation of endogenous circadian patterns of Nrf2, CAT and GPx mRNA levels, antioxidant enzymes activity, and GSH levels. Understanding the age-related loss of circadian rhythmicity of antioxidant defenses in heart, could lead to advancements into preventive and chronotherapeutic treatment of cardiovascular diseases.