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

被引:76
作者
Borchi, Elisabetta [1 ]
Bargelli, Valentina [1 ]
Stillitano, Francesca [2 ]
Giordano, Carla [3 ]
Sebastiani, Mariangela [3 ]
Nassi, Paolo Antonio [1 ]
d'Amati, Giulia [3 ]
Cerbai, Elisabetta [2 ]
Nediani, Chiara [1 ]
机构
[1] Univ Florence, Dept Biochem Sci, I-50134 Florence, Italy
[2] Univ Florence, Dept Preclin & Clin Pharmacol, I-50134 Florence, Italy
[3] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2010年 / 1802卷 / 03期
关键词
NADPH oxidase; Catalase; Glutathione peroxidase; Mn superoxide dismutase; Heart failure; RIGHT-VENTRICULAR FUNCTION; ASSIST DEVICE SUPPORT; OXIDATIVE STRESS; NAD(P)H OXIDASE; ANGIOTENSIN-II; CARDIAC-HYPERTROPHY; C-ABL; OXYGEN; ACTIVATION; CATALASE;
D O I
10.1016/j.bbadis.2009.10.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:331 / 338
页数:8
相关论文
共 39 条
  • [1] AEBI H, 1984, METHOD ENZYMOL, V105, P121
  • [2] NADPH oxidase signaling and cardiac myocyte function
    Akki, Ashwin
    Zhang, Min
    Murdoch, Colin
    Brewer, Alison
    Shah, Ajay M.
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2009, 47 (01) : 15 - 22
  • [3] Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure - A primary role of mechanical unloading underlying reverse remodeling
    Barbone, A
    Holmes, JW
    Heerdt, PM
    The', AHS
    Naka, Y
    Joshi, N
    Daines, M
    Marks, AR
    Oz, MC
    Burkhoff, D
    [J]. CIRCULATION, 2001, 104 (06) : 670 - 675
  • [4] Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy
    Bäumer, AT
    Flesch, M
    Wang, XK
    Shen, QC
    Feuerstein, GZ
    Böhm, M
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2000, 32 (01) : 121 - 130
  • [5] The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology
    Bedard, Karen
    Krause, Karl-Heinz
    [J]. PHYSIOLOGICAL REVIEWS, 2007, 87 (01) : 245 - 313
  • [6] Borchi E., 2008, J CELL MOL MED
  • [7] Right ventricular dysfunction in chronic dilated cardiomyopathy and heart failure
    Brieke, A
    DeNofrio, D
    [J]. CORONARY ARTERY DISEASE, 2005, 16 (01) : 5 - 11
  • [8] Byrne JA, 2003, ARCH MAL COEUR VAISS, V96, P214
  • [9] Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases
    Cao, C
    Leng, YM
    Huang, W
    Liu, X
    Kufe, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (41) : 39609 - 39614
  • [10] Catalase activity is regulated by c-Abl and Arg in the oxidative stress response
    Cao, C
    Leng, YM
    Kufe, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (32) : 29667 - 29675