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Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2017 Dec; Vol. 21 (12), pp. 3420-3434. Date of Electronic Publication: 2017 Jun 23. - Publication Year :
- 2017
-
Abstract
- Catalase is an antioxidative enzyme that converts hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ) produced by superoxide dismutase from highly reactive superoxide (O <subscript>2</subscript> <superscript>-</superscript> ) to water and oxygen molecules. Although recent findings demonstrate that catalase, autophagy and the nuclear factor κB (NF-κB) signalling pathway are centrally involved in diabetic cardiomyopathy (DCM), the interplay between the three has not been fully characterized. Thus, the mechanism responsible for catalase-mediated protection against heart injury in diabetic mice was investigated in this study, as well as the role of NF-κB-p65 in the regulation of autophagic flux was investigated in this study. Western blot analysis revealed that catalase inhibited NF-κB activity and decreased LC3-II (microtubule-associated protein 1 light chain 3) and beclin-1 (Atg6) expression. Furthermore, up-regulation of autophagy was detrimental for cardiac function in diabetic mice. Catalase overexpression reduced the level of NF-κB subunit in the nucleus, where it initiates autophagy through activation of the key autophagy gene BECN1. To evaluate the role of the NF-κB pathway in diabetes-induced autophagy, Bay11-7082, an NF-κB inhibitor, was injected into diabetic mice, which suppressed NF-κB and attenuated diabetes-induced autophagy and myocardial apoptosis. In agreement with the in vivo results, Bay11-7082 also inhibited high-glucose-induced activation of NF-κB and the up-regulation of LC3-II and beclin-1 expression in H9c2 cells. In addition, high-glucose-induced activation of autophagic flux and apoptosis were largely attenuated by p65 siRNA, suggesting that catalase ameliorates diabetes-induced autophagy, at least in part by increasing the activity of the NF-κB pathway and p65-mediated transcription of BECN1.<br /> (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Animals
Apoptosis drug effects
Autophagy drug effects
Beclin-1 metabolism
Catalase metabolism
Cell Line
Diabetes Mellitus, Experimental chemically induced
Diabetes Mellitus, Experimental enzymology
Diabetes Mellitus, Experimental pathology
Diabetic Cardiomyopathies chemically induced
Diabetic Cardiomyopathies enzymology
Diabetic Cardiomyopathies pathology
Gene Expression Regulation
Glucose pharmacology
Male
Mice
Mice, Transgenic
Microtubule-Associated Proteins metabolism
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Nitriles pharmacology
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
Streptozocin
Sulfones pharmacology
Transcription Factor RelA antagonists & inhibitors
Transcription Factor RelA metabolism
Transcription, Genetic
Beclin-1 genetics
Catalase genetics
Diabetes Mellitus, Experimental genetics
Diabetic Cardiomyopathies genetics
Microtubule-Associated Proteins genetics
Transcription Factor RelA genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 21
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28643395
- Full Text :
- https://doi.org/10.1111/jcmm.13252