FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway.
BACKGROUND
Lately, there is accumulating evidence that the Wnt/Frizzled pathway is reactivated after myocardial infarction, the inhibition of the pathway is beneficial since it reduce of myocardial apoptosis and prevents heart failure. FrzA/Sfrp-1, a secreted frizzled-related protein and antagonist for the wnt/frizzled pathway. We assessed the hypothesis that FrzA protects cardiomyocytes from H2O2-Induced Oxidative damage through the inhibition of Wnt/Frizzled pathway activity.


METHODS
We used a recombinant AAV9 vector to deliver FrzA gene into neonatal rat ventricle myocytes and developed an oxidative stress model using H2O2. The cell vitality was measured by MTT colorimetric assay. Western blot and RT-PCR were used to evaluate the expressions of Dvl-1, β-catenin, c-Myc, Bax and Bcl-2. Flow cytometry analysis of cardiomyocytes apoptosis.


RESULTS
We confirmed that Wnt/frizzled pathway is involved in H2O2-induced apoptosis in cardiomyocytes. Compared with controls, H2O2 induced the upregulation of Dvl-1, β-catenin, and c-Myc. FrzA suppressed the expression of Dvl-1, β-catenin, c-Myc and the activity of the Wnt/frizzled pathway. Furthermore, FrzA over-expression decreased the apoptotic rate, and the Bax/Bcl-2 ratio in cardiomyocytes treated with H2O2.


CONCLUSIONS
FrzA, through the inhibition of Wnt/Frizzled pathway activity reduced H2O2-induced cardiomyocytes apoptosis and could be a potential therapeutic target for prevention of cardiac oxidative damage.
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. 709644308@qq.com.
Jing
J
Tao
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, P.R. China. 825116852@qq.com.
Bang-dang
BD
Chen
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. myt-xj@163.com.
Yi-tong
YT
Ma
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. yangyn5126@163.com.
Yi-ning
YN
Yang
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. lxm@163.com.
Xiao-mei
XM
Li
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. max525@163.com.
Xiang
X
Ma
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. 124398024@qq.com.
Zi-xiang
ZX
Yu
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, P.R. China. 604760840@qq.com.
Fen
F
Liu
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. 782073521@qq.com.
Yang
Y
Xiang
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P.R. China. chenyou@126.com.
You
Y
Chen
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D000072261:Dishevelled Proteins; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D006861:Hydrogen Peroxide; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; C494828:Bax protein, rat; C495268:Ctnnb1 protein, rat; C000606580:Dvl1 protein, rat; C500646:Sfrp1 protein, rat; D000094742:Secreted Frizzled-Related Proteins