Catalase ameliorates diabetes‐induced cardiac injury through reduced p65/RelA‐ mediated transcription of BECN1

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.