title: Glutathione metabolic status in the aged rabbit aorta.
abstract: It is not known whether aging alters glutathione metabolic status of the mammalian arterial tissue favoring vascular oxidative stress and dysfunction. Thus we assessed total, reduced and oxidized glutathione (TG, GSH and GSSG, respectively), the glutathione redox ratio (GRR, namely [GSSG]/[GSH+2GSSG]×100), and the activities of the glutathione status-regulating enzymes glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS) and γ-glutamyl transpeptidase (γ-GT) in the aortic tissue of 9 young adult control rabbits (YACR, about 4months old) and 9 aged rabbits (AR, about 4.5years old); aortic lipid and protein oxidation and H2O2were also determined as oxidative stress indicators. Vascular function was assessed on aortic ring preparations. TG and GSH concentrations, together with γ-GCS and γ-GT activities, were significantly lower, while GSSG content and the GRR higher, in the AR than in the YACR aortas; GSSG-Red activity did not differ significantly between the two groups. Heightened levels of lipid and protein oxidation and H2O2occurred in the AR aortas, indicating age-dependent vascular oxidative stress. Moreover, in the whole population of 18 rabbits, the aortic values of GSH and related enzyme activities were inversely and significantly correlated with those of lipid and protein oxidation and H2O2, highlighting the antioxidant role of GSH and related enzymes in the vascular tissue. Aortic endothelium-dependent vasodilation was lower in the AR than in the YACR. In conclusion, glutathione metabolic status is altered in the aged rabbit aorta reflecting depressed γ-GCS- and γ-GT-related GSH biosynthesis and GSSG burden eventually favoring vascular oxidative stress and dysfunction.
authors.affiliation: Dipartimento di Medicina e Scienze dell'Invecchiamento, and Laboratorio di Fisiopatologia dello Stress Ossidativo, Centro Scienze dell'Invecchiamento e Medicina Traslazionale (CeSI-MeT), Center of Excellence on Aging, Università degli Studi "G. d'Annunzio" Chieti Pescara, 66100 Chieti, Italy. Electronic address: dlapenna@unich.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Lapenna
authors.affiliation: Dipartimento di Medicina e Scienze dell'Invecchiamento, and Laboratorio di Fisiopatologia dello Stress Ossidativo, Centro Scienze dell'Invecchiamento e Medicina Traslazionale (CeSI-MeT), Center of Excellence on Aging, Università degli Studi "G. d'Annunzio" Chieti Pescara, 66100 Chieti, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ciofani
authors.affiliation: Dipartimento di Medicina e Scienze dell'Invecchiamento, and Laboratorio di Fisiopatologia dello Stress Ossidativo, Centro Scienze dell'Invecchiamento e Medicina Traslazionale (CeSI-MeT), Center of Excellence on Aging, Università degli Studi "G. d'Annunzio" Chieti Pescara, 66100 Chieti, Italy.
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Giamberardino
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D016014:Linear Models; D050356:Lipid Metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011817:Rabbits; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D006861:Hydrogen Peroxide; D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Aging; Glutathione; Glutathione reductase; Lipid and protein oxidation; Oxidative stress; Rabbit aorta; γ-Glutamyl transpeptidase; γ-Glutamylcysteine synthetase