Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; Department of Free Radical Pathophysiology, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Arch Biochem Biophys. 2019 Aug 15;671:18-26. doi: 10.1016/j.abb.2019.06.001. Epub 2019 Jun 6.
P38alpha kinase plays an important role in the regulation of both cell stress response and cell fate. In this study, we report that p38alpha kinase-deficient embryonic stem cells exhibit a higher production of reactive oxygen species (ROS) in contrast to their wild-type counterpart. Analysis of the expressions of NADPH oxidases (NOXs) and dual oxidases, crucial enzymes involved in intracellular ROS formation, shows NOX2/gp91 is over-expressed in p38alpha deficient cells. The particular increase in superoxide formation was confirmed by the specific detection of hydroethidine derivate 2-hydroxyethidium. ROS formation decreased when the level of NOX2 was silenced by siRNA in p38alpha deficient cells. These data suggest the importance of p38alpha kinase in the regulation of ROS metabolism in embryonic stem cells and the significance of the observed phenomena of cancer cell-like phenotypes, which is discussed.
p38α 激酶在细胞应激反应和细胞命运的调节中起着重要作用。在这项研究中，我们报告说 p38α 激酶缺陷型胚胎干细胞产生的活性氧（ROS）明显高于其野生型对应物。对参与细胞内 ROS 形成的关键酶 NADPH 氧化酶（NOXs）和双氧化酶的表达分析表明，p38α 缺陷细胞中 NOX2/gp91 过表达。通过特异性检测羟乙基二氢乙锭衍生物 2-羟乙基乙锭，证实了超氧化物形成的特殊增加。当用 siRNA 沉默 p38α 缺陷细胞中的 NOX2 水平时，ROS 形成减少。这些数据表明 p38α 激酶在胚胎干细胞 ROS 代谢调节中的重要性，以及所观察到的类似癌细胞表型现象的意义，对此进行了讨论。
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