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首页> 外文期刊>Cellular Physiology and Biochemistry >Depletion of 14-3-3 protein exacerbates cardiac oxidative stress, inflammation and remodeling process via modulation of MAPK/NF-κB signaling pathways after streptozotocin-induced diabetes mellitus
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Depletion of 14-3-3 protein exacerbates cardiac oxidative stress, inflammation and remodeling process via modulation of MAPK/NF-κB signaling pathways after streptozotocin-induced diabetes mellitus

机译：14-3-3蛋白的消耗通过链脲佐菌素诱导的糖尿病后MAPK /NF-κB信号通路的调节加剧了心脏的氧化应激，炎症和重塑过程。

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Diabetic cardiomyopathy is associated with increased oxidative stress and inflammation. Mammalian 14-3-3 proteins are dimeric phosphoserine-binding proteins that participate in signal transduction and regulate several aspects of cellular biochemistry. The aim of the study presented here was to clarify the role of 14-3-3 protein in the mitogen activated protein kinase (MAPK) and nuclear factor-kB (NF-κB) signaling pathway after experimental diabetes by using transgenic mice with cardiac-specific expression of a dominant-negative 14-3-3 protein mutant (DN 14-3-3). Significant p-p38 MAPK activation in DN 14-3-3 mice compared to wild type mice (WT) after diabetes induction and with a corresponding up regulation of its downstream effectors, p-MAPK activated protein kinase 2 (MAPKAPK-2). Marked increases in cardiac hypertrophy, fibrosis and inflammation were observed with a corresponding up-regulation of atrial natriuretic peptide, osteopontin, connective tissue growth factor, tumor necrosis factor α, interleukin (IL)-1β, IL-6 and cellular adhesion molecules. Moreover, reactive oxygen species, left ventricular expression of NADPH oxidase subunits, p22 phox, p67 phox, and Nox4, and lipid peroxidation levels were significantly increased in diabetic DN 14-3-3mice compared to diabetic WT mice. Furthermore, myocardial NF-κB activation, inhibitor of kappa B-α degradation and mRNA expression of proinflammatory cytokines were significantly increased in DN 14-3-3 mice compared to WT mice after diabetes induction. In conclusion, our data suggests that depletion of 14-3-3 protein induces cardiac oxidative stress, inflammation and remodeling after experimental diabetes induction mediated through p38 MAPK, MAPKAPK-2 and NF-κB signaling.
机译：糖尿病性心肌病与氧化应激和炎症增加有关。哺乳动物14-3-3蛋白是二聚体磷酸丝氨酸结合蛋白，参与信号转导并调节细胞生物化学的多个方面。此处进行研究的目的是，通过使用具有心脏造血功能的转基因小鼠，来阐明14-3-3蛋白在实验性糖尿病后在丝裂原活化蛋白激酶（MAPK）和核因子-kB（NF-κB）信号传导途径中的作用。显性阴性14-3-3蛋白突变体（DN 14-3-3）的特异性表达。与野生型小鼠（WT）相比，DN 14-3-3小鼠中的p-p38 MAPK活化显着高于糖尿病诱导后的野生型小鼠（WT），并且其下游效应子p-MAPK活化的蛋白激酶2（MAPKAPK-2）有相应的上调。观察到心脏肥大，纤维化和炎症明显增加，相应的心房利钠肽，骨桥蛋白，结缔组织生长因子，肿瘤坏死因子α，白介素（IL）-1β，IL-6和细胞粘附分子上调。此外，与糖尿病WT小鼠相比，糖尿病DN 14-3-3小鼠的活性氧，NADPH氧化酶亚基的左心室表达，p22 phox，p67 phox和Nox4以及脂质过氧化水平显着增加。此外，与糖尿病诱导后的WT小鼠相比，DN 14-3-3小鼠的心肌NF-κB活化，κB-α降解抑制剂和促炎细胞因子的mRNA表达显着增加。总之，我们的数据表明，通过p38 MAPK，MAPKAPK-2和NF-κB信号传导介导的实验性糖尿病诱导后，14-3-3蛋白的消耗会诱导心脏氧化应激，炎症和重塑。

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