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 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.
School of Pharmaceutical Science, Jiangnan University, Wuxi, P.R. China.
Jia
J
Zhou
State Key Laboratory of Natural Medicines, Center of Drug discovery, China Pharmaceutical University, Nanjing, P.R. China.
Yi-Hua
YH
Zhang
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, P.R. China.
Hui-Zhu
HZ
Song
State Key Laboratory of Natural Medicines, Center of Drug discovery, China Pharmaceutical University, Nanjing, P.R. China.
Hui
H
Ji
School of Pharmaceutical Science, Jiangnan University, Wuxi, P.R. China.
Xiao-Li
XL
Wang
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, P.R. China.
Lei
L
Wang
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, P.R. China.
Jun
J
Qian
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, P.R. China.
Jing-Jing
JJ
Ling
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, P.R. China.
Feng-Feng
FF
Ping
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D001572:Benzofurans; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C027125:3-n-butylphthalide; D019255:NADPH Oxidases; D047390:Casein Kinase II; D020830:rac1 GTP-Binding Protein
5d; CK2; NADPH oxidase; Neuroscience; ROS; neuroprotection