Open AccessCatalase ameliorates diabetes‐induced cardiac injury through reduced p65/RelA‐ mediated transcription of BECN1
Author(s) -
Wang Xu,
Tao Youli,
Huang Yewei,
Zhan Kungao,
Xue Mei,
Wang Ying,
Ruan Dandan,
Liang Yangzhi,
Huang Xiaozhong,
Lin Jianjun,
Chen Zhiwei,
Lv Lingchun,
Li Santie,
Chen Gen,
Wang Yang,
Chen Ruijie,
Cong Weitao,
Jin Litai
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13252
Subject(s) - becn1 , autophagy , diabetic cardiomyopathy , catalase , superoxide dismutase , reactive oxygen species , chemistry , microbiology and biotechnology , western blot , apoptosis , nf κb , small interfering rna , biology , medicine , oxidative stress , biochemistry , transfection , cardiomyopathy , heart failure , gene
Catalase is an antioxidative enzyme that converts hydrogen peroxide (H 2 O 2 ) produced by superoxide dismutase from highly reactive superoxide (O 2 − ) 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.