FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway.
FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway.
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FrzA 基因通过抑制 Wnt/Frizzled 通路来保护心肌细胞免受 H2O2 诱导的氧化应激。
DOI：
10.1186/s12944-015-0088-0
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发表时间：
2015-08-18
影响因子：
4.5
通讯作者：
Chen Y
中科院分区：
文献类型：
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作者：
Tao J;Chen BD;Ma YT;Yang YN;Li XM;Ma X;Yu ZX;Liu F;Xiang Y;Chen Y
近年来，越来越多的证据表明，心肌梗死后Wnt/Frizzled通路重新激活，抑制该通路可减少心肌细胞凋亡，预防心力衰竭。FrzA/Sfrp-1，一种分泌型卷曲相关蛋白和wnt/frizzled通路的拮抗剂。我们评估的假设，FrzA保护心肌细胞H2 O2诱导的氧化损伤，通过抑制Wnt/Frizzled pathway activity.MethodsWe使用重组AAV 9载体，将FrzA基因导入新生大鼠心室肌细胞，并开发了一个氧化应激模型，使用H2 O2。MTT比色法测定细胞活力。Western blot和RT-PCR检测Dvl-1、β-catenin、c-Myc、Bax和Bcl-2的表达。流式细胞术分析心肌细胞凋亡。结果我们证实，Wnt/frizzled途径参与H2 O2诱导的心肌细胞凋亡。与对照组相比，H2 O2诱导Dvl-1、β-catenin和c-Myc上调。FrzA抑制Dvl-1、β-catenin、c-Myc的表达和Wnt/frizzled通路的活性。结论FrzA通过抑制Wnt/Frizzled通路活性，减少H2 O2诱导的心肌细胞凋亡，可能成为预防心肌氧化损伤的潜在治疗靶点。
BackgroundLately, 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.MethodsWe 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.ResultsWe confirmed that Wnt/frizzled pathway is involved in H2O2-induced apoptosis in cardiomyocytes. Compared with controls, H2O2induced 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.ConclusionsFrzA, 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.