Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, D-06097 Halle, Germany.
Julius-Bernstein-Institut für Physiologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, D-06097 Halle, Germany.
Int J Mol Sci. 2022 Apr 23;23(9):4688. doi: 10.3390/ijms23094688.
Reversible protein phosphorylation is a posttranslational modification of regulatory proteins involved in cardiac signaling pathways. Here, we focus on the role of protein phosphatase 2A (PP2A) for cardiac gene expression and stress response using a transgenic mouse model with cardiac myocyte-specific overexpression of the catalytic subunit of PP2A (PP2A-TG). Gene and protein expression were assessed under basal conditions by gene chip analysis and Western blotting. Some cardiac genes related to the cell metabolism and to protein phosphorylation such as kinases and phosphatases were altered in PP2A-TG compared to wild type mice (WT). As cardiac stressors, a lipopolysaccharide (LPS)-induced sepsis in vivo and a global cardiac ischemia in vitro (stop-flow isolated perfused heart model) were examined. Whereas the basal cardiac function was reduced in PP2A-TG as studied by echocardiography or as studied in the isolated work-performing heart, the acute LPS- or ischemia-induced cardiac dysfunction deteriorated less in PP2A-TG compared to WT. From the data, we conclude that increased PP2A activity may influence the acute stress tolerance of cardiac myocytes.
蛋白质可逆磷酸化是一种参与心脏信号通路的调节蛋白的翻译后修饰。在这里，我们使用心肌细胞特异性过表达蛋白磷酸酶 2A（PP2A）催化亚基的转基因小鼠模型，重点研究 PP2A 在心脏基因表达和应激反应中的作用（PP2A-TG）。通过基因芯片分析和 Western blot 检测在基础条件下的基因和蛋白质表达。与野生型（WT）小鼠相比，PP2A-TG 中的一些与细胞代谢和蛋白质磷酸化相关的心脏基因，如激酶和磷酸酶发生了改变。作为心脏应激源，体内脂多糖（LPS）诱导的败血症和体外整体心脏缺血（停流分离灌流心脏模型）进行了检查。尽管通过超声心动图或在分离工作心脏中研究，PP2A-TG 中的基础心脏功能降低，但与 WT 相比，急性 LPS 或缺血诱导的心脏功能障碍恶化程度较轻。从这些数据中，我们得出结论，增加的 PP2A 活性可能影响心肌细胞的急性应激耐受性。
