EFFECT OF AGING ON THE CIRCADIAN PATTERNS OF ANTIOXIDANT ENZYMES IN HEART

ALTAMIRANO FG; FERRAMOLA, M.; CASTRO-PASCUAL, I; ANZULOVICH AC; LACOSTE MG

Estancia Grande (San Luis)

Congreso; XXXII Reunion Anual de la Soc. de Biol. 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 control (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. Genes? regulatory regions were scanned for putative clock-responsive sites using a bioinformatic tool. GSH levels were measured by colorimetric assay. E-box (CANNTG) sites were found on regulatory regions of Nrf2, GPx and CAT genes. The expression of Nrf2, as well as the expression and activity of the antioxidant enzymes vary significantly in a 24h period under constant darkness conditions. We also observed temporal variation of GSH levels. Interestingly, aging abolishes the endogenous oscillation of Nrf2, CAT and GPx mRNA and the enzymatic activity, as well as the GSH levels. Understanding the age-related circadian declining of the endogenous defense system in heart, could lead to advancements into preventive and chronotherapeutic treatment of cardiovascular diseases.