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Activation of nuclear β-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy.
Biochem Biophys Res Commun. 2017 12 02; 493(4):1573-1580.BB

Abstract

Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/β-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with β-catenin in DCM remains elusive. This study intended to explore the effect of β-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 β-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 β-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 β-catenin/c-Myc axis, not only did siRNA knockdown of β-catenin or c-Myc attenuate cell injury in H2O2-stimulated cardiomyocytes, but also diabetic cardiac-specific β-catenin-knockout mice displayed the same prevention of heart injury as insulin-treated diabetic mice. The present study demonstrated that activated nuclear β-catenin/c-Myc axis was responsible for oxidative cardiac impairment of DCM. Therefore, repressing functional nuclear β-catenin may provide a hopeful therapeutic strategy for DCM.

Authors+Show Affiliations

Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai 200120, China. Electronic address: liupengdoctor@126.com.College of Clinical Medicine, Shanxi Medical University, Taiyuan 030001, China.Department of Orthopaedics, Shaanxi Provincial People's Hospital, Xi'an Jiaotong University, Xi'an 710068, China.Department of Internal Medicine, Shanghai Dermatology Hospital, Tongji University, Shanghai 200443, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28989026

Citation

Liu, Peng, et al. "Activation of Nuclear β-catenin/c-Myc Axis Promotes Oxidative Stress Injury in Streptozotocin-induced Diabetic Cardiomyopathy." Biochemical and Biophysical Research Communications, vol. 493, no. 4, 2017, pp. 1573-1580.
Liu P, Su J, Song X, et al. Activation of nuclear β-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy. Biochem Biophys Res Commun. 2017;493(4):1573-1580.
Liu, P., Su, J., Song, X., & Wang, S. (2017). Activation of nuclear β-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy. Biochemical and Biophysical Research Communications, 493(4), 1573-1580. https://doi.org/10.1016/j.bbrc.2017.10.027
Liu P, et al. Activation of Nuclear β-catenin/c-Myc Axis Promotes Oxidative Stress Injury in Streptozotocin-induced Diabetic Cardiomyopathy. Biochem Biophys Res Commun. 2017 12 2;493(4):1573-1580. PubMed PMID: 28989026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of nuclear β-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy. AU - Liu,Peng, AU - Su,Jianfang, AU - Song,Xixi, AU - Wang,Shixiao, Y1 - 2017/10/06/ PY - 2017/09/28/received PY - 2017/10/05/accepted PY - 2017/10/11/pubmed PY - 2017/10/31/medline PY - 2017/10/10/entrez KW - Apoptosis KW - DNA damage KW - Diabetic cardiomyopathy KW - Oxidative stress KW - c-Myc KW - β-catenin SP - 1573 EP - 1580 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 493 IS - 4 N2 - Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/β-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with β-catenin in DCM remains elusive. This study intended to explore the effect of β-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 β-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 β-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 β-catenin/c-Myc axis, not only did siRNA knockdown of β-catenin or c-Myc attenuate cell injury in H2O2-stimulated cardiomyocytes, but also diabetic cardiac-specific β-catenin-knockout mice displayed the same prevention of heart injury as insulin-treated diabetic mice. The present study demonstrated that activated nuclear β-catenin/c-Myc axis was responsible for oxidative cardiac impairment of DCM. Therefore, repressing functional nuclear β-catenin may provide a hopeful therapeutic strategy for DCM. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/28989026/Activation_of_nuclear_β_catenin/c_Myc_axis_promotes_oxidative_stress_injury_in_streptozotocin_induced_diabetic_cardiomyopathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(17)31989-7 DB - PRIME DP - Unbound Medicine ER -