Activation of Nrf2-ARE pathway in brain after traumatic brain injury.
Secondary brain injury plays a pivotal role in the outcome of patients suffering from traumatic brain injury (TBI). The mechanisms underlying secondary brain injury are complex and interrelated. Previous studies focused on one of these mechanisms have been proved to be ineffective in clinical practice. Therefore, a target, which can interrupt multi-mechanisms underlying TBI, is desirable. Nrf2-ARE pathway has been proved to be the key regulator in reducing oxidative stress, inflammatory damage and accumulation of toxic metabolites, which are all involved in TBI. However, whether Nrf2-ARE pathway is activated after TBI has not been studied. In the present study, the nuclear Nrf2 protein level was detected by Western blot, and the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1), two Nrf2-regulated gene products, were determined using reverse-transcriptase polymerase chain reaction (RT-PCR) 24h after TBI. Furthermore, we also localized the expression of Nrf2 and HO-1 using immunohistochemical study. After TBI, the nuclear Nrf2 protein level was significantly increased, and the mRNA levels of both HO-1 and NQO1 were also up regulated. Moreover, both Nrf2 and HO-1 were localized in the same types of cells. According to these results, it could be postulated that Nrf2-ARE pathway was activated in brain after TBI.
Yan
Wei
W
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China.
Wang
Han-Dong
HD
Hu
Zhi-Gang
ZG
Wang
Qing-Feng
QF
Yin
Hong-Xia
HX
D000818:Animals; D001921:Brain / Q000201:enzymology*; D001930:Brain Injuries / Q000473:pathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D054464:Peroxiredoxins; D051547:Heme Oxygenase-1