5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury.
5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury.
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5d 是 3-正丁基苯酞的新型类似物，通过缺血/再灌注损伤后 CK2 的正向调节降低 NADPH 氧化酶活性
DOI：
10.18632/oncotarget.8548
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发表时间：
2016-06-28
期刊：
影响因子：
--
通讯作者：
Ping FF
中科院分区：
文献类型：
--
作者：
Zhou J;Zhang YH;Song HZ;Ji H;Wang XL;Wang L;Qian J;Ling JJ;Ping FF
5d 是外消旋 3-正丁基苯酞 (NBP) 的新型类似物，据报道其具有体外自由基清除活性和体内预防性神经保护作用。然而，5天减轻缺血/再灌注（I/R）损伤的机制仍不清楚。我们的结果表明，I/R 损伤后 5d，CK2 活性以及 CK2α 和 2α' 蛋白水平显着增加。此外，5d抑制了胞质p47phox和Rac1向膜的易位，减少了NOX4的表达和ROS的产生。此外，5d阻断CK2α和Rac1之间的解离，从而降低NADPH氧化酶活性。基于这些发现，我们提出5d的神经保护作用是由于CK2活性增加，从而阻断I/R诱导的CK2α和Rac1之间的解离，降低NADPH氧化酶活性，抑制ROS产生，最终实现I/R的神经保护作用。这些发现表明 5d 可能被认为是缺血性中风进一步研究的有吸引力的候选者。
5d, a novel analogue of the racemic 3-n-butylphthalide (NBP), has been reported for its free radical scavenging activity in vitro and preventive neuroprotection in vivo. Nevertheless, the mechanism by which 5d attenuated ischemia/reperfusion (I/R) injury is still unknown. Our results showed that 5d significantly increased CK2 activity as well as CK2α and 2α' protein levels after I/R injury. Besides, 5d suppressed the translocation of cytosolic p47phox and Rac1 to the membrane, decreased NOX4 expression and ROS generation. Furthermore, 5d blocked the dissociation between CK2α and Rac1 so as to decrease NADPH oxidase activity. Based on these findings, we propose that the neuroprotective effect of 5d is due to an increase of CK2 activity, which blocks I/R-induced dissociation between CK2α and Rac1, decreases NADPH oxidase activity, inhibits ROS production and finally realizes the neuroprotection of I/R. These findings point to that 5d might be considered an attractive candidate for further studies in ischemic stroke.
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