title: Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury.
abstract: Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP.
authors: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors: Jia
authors: J
authors: Shen
authors: Xiao-Yin
authors: XY
authors: Bai
authors: Yuan
authors: Y
authors: Qin
authors: Wei-Wei
authors: WW
authors: Jin
authors: Jing-Yin
authors: JY
authors: Zhou
authors: Ji-Ping
authors: JP
authors: Zhou
authors: Ying-Gang
authors: YG
authors: Yan
authors: Qiong
authors: Q
authors: Wang
authors: Iain C
authors: IC
authors: Bruce
authors: Jiang-Hua
authors: JH
authors: Chen
authors: Qiang
authors: Q
authors: Xia
mesh_terms: D000098:Acetophenones; D000818:Animals; D015536:Down-Regulation; D004789:Enzyme Activation; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D015424:Reperfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism*; D013534:Survival; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D005609:Free Radicals; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D013481:Superoxides; C056165:acetovanillone; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020830:rac1 GTP-Binding Protein