A time course of NADPH-oxidase up-regulation and endothelial nitric oxide synthase activation in the hippocampus following neurotrauma.
A time course of NADPH-oxidase up-regulation and endothelial nitric oxide synthase activation in the hippocampus following neurotrauma.
复制标题
DOI：
10.1016/j.freeradbiomed.2014.08.025
复制
发表时间：
2014-12
影响因子：
7.4
通讯作者：
Scheff, Stephen W.
中科院分区：
文献类型：
--
作者：
Ansari, Mubeen A.;Roberts, Kelly N.;Scheff, Stephen W.
烟酰胺腺嘌呤二核苷酸磷酸氧化酶（nadph氧化酶；NOX）是一种复杂的酶，负责增加活性氧（ROS），超氧化物（O2.−）的水平。NOX衍生O2。−是创伤性脑损伤（TBI）后氧化应激和炎症介导的多重继发性损伤级联反应（SIC）的关键参与者。O2。−与一氧化氮（NO）反应，产生各种活性氮（RNS），并导致细胞凋亡。单侧皮质挫伤后，在损伤后的不同时间（1、3、6、12、24、48、72和96小时）杀死年轻成年大鼠。分析海马新鲜组织的NOX活性和O2水平。此外，我们还评估了细胞质内NOX蛋白（p67Phox、p47Phox和p40Phox）在膜上的易位，以及总NO和内皮一氧化氮合酶（p-eNOS）的激活（磷酸化）。结果表明，酶和氧水平。−和NO在海马中具有时间依赖性损伤效应。胞质内NOX蛋白向膜的易位、NOX活性和O2。−也随时间增加。都有，NOX活性和O2。p-eNOS水平在1小时内升高，在TBI后12小时NO显著升高。NO水平与p-eNOS没有显著相关性，但与O2有相关性。氮氧化物的上调与两种氧水平密切相关。-以及总NO。TBI后的最初12小时非常重要，因为这可能是中断SIC的机会窗口。它可能是重要的选择性靶向转运的细胞质亚基的调节氮氧化物的功能。
Nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase; NOX) is a complex enzyme responsible for increased levels of reactive oxygen species (ROS), superoxide (O2.−). NOX derived O2.− is a key player in oxidative stress and inflammation mediated multiple secondary injury cascades (SIC) following traumatic brain injury (TBI). The O2.− reacts with nitric oxide (NO), produces various reactive nitrogen species (RNS), and contributes to apoptotic cell death. Following a unilateral cortical contusion, young adult rats were killed at various times post injury (1, 3, 6, 12, 24, 48, 72, and 96 h). Fresh tissue from the hippocampus was analyzed for NOX activity, and level of O2.−. In addition we evaluated the translocation of cytosolic NOX proteins (p67Phox, p47Phox and p40Phox) to the membrane, along with total NO and the activation (phosphorylation) of endothelial nitric oxide synthase (p-eNOS). Results show that both enzymes and levels of O2.− and NO have time dependent injury effects in the hippocampus. Translocation of cytosolic NOX proteins into membrane, NOX activity and O2.− were also increased in a time dependent fashion. Both, NOX activity and O2.− were increased at 6 h. Levels of p-eNOS increased within 1 h, with significant elevation of NO at 12 h post TBI. Levels of NO failed to show a significant association with p-eNOS, but did associate with O2.−. NOX up-regulation strongly associated with both the levels of O2.− and also total NO. The initial 12 hours post TBI are very important as a possible window of opportunity to interrupt SIC. It may be important to selectively target the translocation of cytosolic subunits for the modulation of NOX function.
登录
查看更多内容
影响因子：
7.4
作者：
Ansari, Mubeen A.;Keller, Jeffrey N.;Scheff, Stephen W.
通讯作者：
Scheff, Stephen W.
影响因子：
2.7
作者：
Chern, Chang-Ming;Liou, Kuo-Tong;Shen, Yuh-Chiang
通讯作者：
Shen, Yuh-Chiang
影响因子：
4.2
作者：
DeWitt, DS;Smith, TG;Prough, DS
通讯作者：
Prough, DS
影响因子：
5.3
作者：
Choi, SH;Lee, DY;Jin, BK
通讯作者：
Jin, BK
影响因子：
5.3
作者：
Abramov, AY;Jacobson, J;Duchen, MR
通讯作者：
Duchen, MR