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J Mol Cell Cardiol. 2015 Dec;89(Pt B):314-25. doi: 10.1016/j.yjmcc.2015.10.010. Epub 2015 Oct 9.

Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.

Author information

1
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, PR China.
2
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, PR China; The Health Examination Center, the 117th Hospital of Chinese People's Liberation Army, Hangzhou 310013, PR China.
3
Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou 325000, PR China.
4
The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.
5
The First Hospital of Jilin University, Changchun 130021, PR China.
6
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address: jin_litai@126.com.
7
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address: ty1791561@163.com.

Abstract

Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration.

KEYWORDS:

Cardiomyopathy; Catalase; Diabetes; NF-κB; Nitration

PMID:
26456065
DOI:
10.1016/j.yjmcc.2015.10.010
[Indexed for MEDLINE]

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