Objectives Recently there is accumulating evidence that the wnt/frizzled pathway may play a distinct role in cardiomyocytes apoptosis. We have demonstrated that staurosporine induces cardiomyocytes apoptosis in vitro. FrzA/sFRP-1, a secreted frizzled-related protein and antagonist for the wnt/frizzled pathway. This study was to explore the role of wnt/frizzled signalling pathway in staurosporine-induced apoptosis in cardiomyocytes and assessed the hypothesis that FrzA overexpression could attenuates staurosporine-induced apoptosis in cardiomyocytes.
Methods We found that the staurosporine induced the expression of Dvl-1 and subsequent up-regulation of b-catenin, which are the downstream members of wnt/frizzled pathway when cardiomyocytes apoptosis occurred. The staurosporine concentration elevated, apoptosis becomes serious and Dvl-1/b-catenin expression enhanced. Then cardiomyocytes were transfected with a recombinant AAV9 vector to deliver the FrzA gene, we found that FrzA gene suppression the expression of Dvl-1 and b-catenin and the activity of the Wnt/ frizzled pathway.
Results FrzA overexpression decreased the apoptotic rate, caspase-3 activity, and the Bax/Bcl-2 ratio in cardiomyocytes treated with staurosporine.
Conclusions Overexpression of FrzA inhibited the activity of the Wnt/frizzled pathway and reduced the apoptosis of cardiomyocytes.