FrzA gene protects cardiomyocytes from H(2)O(2)-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 H(2)O(2)-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 H(2)O(2). 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 H(2)O(2)-induced apoptosis in cardiomyocytes. Compared with controls, H(2)O(2) 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 H(2)O(2). CONCLUSIONS: FrzA, through the inhibition of Wnt/Frizzled pathway activity reduced H(2)O(2)-induced cardiomyocytes apoptosis and could be a potential therapeutic target for prevention of cardiac oxidative damage.