糖原合酶kinase-3beta cardiomyoblasts矩阵metalloproteinase-2激活介导蛋白质水解。
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Kandasamy广告,舒尔茨R
糖原合酶kinase-3beta cardiomyoblasts矩阵metalloproteinase-2激活介导蛋白质水解。
Cardiovasc研究》2009年9月1日,83 (4):698 - 706。doi: 10.1093 /表格/ cvp175。Epub 2009年6月3。
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19493954 (在PubMed]
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目的:基质金属蛋白酶(MMP) 2导致心肌氧化应激损伤sarcomeric退化和细胞骨架蛋白在心肌细胞。糖原合酶激酶(GSK) 3β在氧化应激和容易特异表达蛋白水解乳沟。我们决定GSK-3beta是否MMP-2衬底作为氧化应激的结果。方法和结果:MMP-2和GSK-3beta孵化和乳沟片段被免疫印迹和银染色鉴定。完整的蛋白质和其主要裂解片段受到胰蛋白酶消化和合成肽被质/ MS分析。GSK-3beta激酶活性测定使用肽底物和γ- (32)P atp。氧化应激在H9c2 cardiomyoblasts诱导了H (2) O(2)和MMP-2和GSK-3beta测量水平和活动。孵化的47 kDa GSK-3beta MMP-2导致时间和concentration-dependant乳沟GSK-3beta大约30 kDa的外表看到的片段。MS分析和吉祥物数据库搜索产生的肽的氨基酸序列GSK-3beta必威国际app缺乏氨基地区。GSK-3beta激酶活性显著增加在孵化了MMP-2废除的MMP抑制剂gm - 6001。 H(2)O(2) challenge of H9c2 cardiomyoblasts significantly increased the activity and level of MMP-2, reduced the level of GSK-3beta, and significantly increased GSK-3beta kinase activity. Both the loss of intact GSK-3beta and increase in its kinase activity were reduced with MMP inhibitors. MMP-2 pull-down assays in H9c2 cell lysates showed the association of MMP-2 with GSK-3beta. CONCLUSION: GSK-3beta may be a target of MMP-2 and its cleavage by MMP-2 enhances its kinase activity. MMP-2 may cleave off the N-terminal of GSK-3beta where the inhibitory phosphorylation of serine-9 occurs. MMP-2-mediated augmentation of GSK-3beta kinase activity may contribute to cardiac injury resulting from enhanced oxidative stress.