| First Author | Liu P | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 493 |
| Issue | 4 | Pages | 1573-1580 |
| PubMed ID | 28989026 | Mgi Jnum | J:250749 |
| Mgi Id | MGI:6103242 | Doi | 10.1016/j.bbrc.2017.10.027 |
| Citation | Liu P, et al. (2017) Activation of nuclear beta-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy. Biochem Biophys Res Commun 493(4):1573-1580 |
| abstractText | Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/beta-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with beta-catenin in DCM remains elusive. This study intended to explore the effect of beta-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining. Nuclear beta-catenin activity and oxidative damage degree were measured by western blotting, qPCR, MTT assay and TUNEL staining. Cardiac function and morphology were evaluated by echocardiography and histopathology. Under diabetic oxidative stress or H2O2 stimulation, nuclear beta-catenin accumulation upregulated downstream c-Myc and further facilitated DNA damage and p53-mediated apoptosis as well as cell viability reduction, followed by phenotypic changes of cardiac dysfunction, interstitial fibrosis deposition and myocardial atrophy. Conversely, through directly inhibiting nuclear beta-catenin/c-Myc axis, not only did siRNA knockdown of beta-catenin or c-Myc attenuate cell injury in H2O2-stimulated cardiomyocytes, but also diabetic cardiac-specific beta-catenin-knockout mice displayed the same prevention of heart injury as insulin-treated diabetic mice. The present study demonstrated that activated nuclear beta-catenin/c-Myc axis was responsible for oxidative cardiac impairment of DCM. Therefore, repressing functional nuclear beta-catenin may provide a hopeful therapeutic strategy for DCM. |
