In pathological conditions, the balance between reactive oxygen species (ROS) and antioxidants may shift toward a relative increase of ROS, resulting in oxidative stress. Conflicting data are available on antioxidant defenses in human failing heart and they are limited to the left ventricle. Thus, we aimed to investigate and compare the source of oxidant and antioxidant enzyme activities in the right (RV) and left (LV) ventricles of human failing hearts. We found a significant increase in superoxide production only by NADPH oxidase in both failing ventricles, more marked in RV. Despite unchanged mRNA or protein expression, catalase (CAT) and glutathione peroxidase (GPx) activities were increased, and their increases reflected the levels of Tyr phosphorylation of the respective enzyme. Manganese superoxide dismutase (Mn-SOD) activity appeared unchanged. The increase in NADPH oxidase-dependent superoxide production positively correlated with the activation of both CAT and GPx. However, the slope of the linear correlation (m) was steeper in LV than in RV for GPx (LV: m=2.416; RV: m=1.485) and CAT (LV: m=1.007; RV: m=0.354). Accordingly, malondialdehyde levels, an indirect index of oxidative stress, were significantly higher in the RV than LV. We conclude that in human failing RV and LV, oxidative stress is associated with activation of antioxidant enzyme activity. This activation is likely due to post-translational modifications and more evident in LV. Overall, these findings suggest a reduced protection of RV against oxidative stress and its potential contribution to the progression toward overt heart failure.

Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure / E. Borchi; V. Bargelli; F. Stillitano; C. Giordano; M. Sebastiani; PA. Nassi; G.d'Amati; E .Cerbai; C. Nediani. - In: BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE. - ISSN 0925-4439. - ELETTRONICO. - 1802:(2010), pp. 331-338. [10.1016/j.bbadis.2009.10.014]

Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure

BORCHI, ELISABETTA;STILLITANO, FRANCESCA;NASSI, PAOLO ANTONIO;CERBAI, ELISABETTA;NEDIANI, CHIARA
2010

Abstract

In pathological conditions, the balance between reactive oxygen species (ROS) and antioxidants may shift toward a relative increase of ROS, resulting in oxidative stress. Conflicting data are available on antioxidant defenses in human failing heart and they are limited to the left ventricle. Thus, we aimed to investigate and compare the source of oxidant and antioxidant enzyme activities in the right (RV) and left (LV) ventricles of human failing hearts. We found a significant increase in superoxide production only by NADPH oxidase in both failing ventricles, more marked in RV. Despite unchanged mRNA or protein expression, catalase (CAT) and glutathione peroxidase (GPx) activities were increased, and their increases reflected the levels of Tyr phosphorylation of the respective enzyme. Manganese superoxide dismutase (Mn-SOD) activity appeared unchanged. The increase in NADPH oxidase-dependent superoxide production positively correlated with the activation of both CAT and GPx. However, the slope of the linear correlation (m) was steeper in LV than in RV for GPx (LV: m=2.416; RV: m=1.485) and CAT (LV: m=1.007; RV: m=0.354). Accordingly, malondialdehyde levels, an indirect index of oxidative stress, were significantly higher in the RV than LV. We conclude that in human failing RV and LV, oxidative stress is associated with activation of antioxidant enzyme activity. This activation is likely due to post-translational modifications and more evident in LV. Overall, these findings suggest a reduced protection of RV against oxidative stress and its potential contribution to the progression toward overt heart failure.
2010
1802
331
338
Goal 3: Good health and well-being for people
E. Borchi; V. Bargelli; F. Stillitano; C. Giordano; M. Sebastiani; PA. Nassi; G.d'Amati; E .Cerbai; C. Nediani
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/368082
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