title: Alterations in the time course of expression of the Nox family in the brain in a rat experimental cerebral ischemia and reperfusion model: effects of melatonin.
abstract: Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS), which results in a poor prognosis for ischemic stroke patients. This study was designed to evaluate the time course of expression of the Nox family, a major source of ROS, and whether melatonin, a potent scavenger of ROS, influences these parameters in a rat model of cerebral I/R caused by middle cerebral artery occlusion (MCAO). After 2-hr occlusion, the filament was withdrawn to allow reperfusion. At 0, 3, 6, 12, 24, and 48 hr after reperfusion, brain tissue samples were obtained for assays. Among the Nox family, the mRNA and protein levels of Nox2 and Nox4 were increased both in the ischemic hemisphere and contralateral counterpart in the experimental I/R rats at 0 hr after reperfusion, peaked at 3 hr, and then returned to the basal level at 24 hr. Double-immunofluorescence staining further confirmed the expressions of Nox2 and Nox4 in three major types of brain cells, including neurons, astrocytes, and endothelial cells. In addition, melatonin (5 mg/kg) or its vehicle was injected intraperitoneally at 0.5 hr before MCAO. Compared with I/R + vehicle group, melatonin pretreatment diminished the increased expression of Nox2 and Nox4, reduced ROS levels, and inhibited cell apoptosis. Our findings suggested that the inhibition of Nox2 and Nox4 expressions by melatonin may essentially contribute to its antioxidant and anti-apoptotic effects during brain I/R.
authors.affiliation: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Dongxia
authors.initials: D
authors.lastname: Feng
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Anju
authors.initials: A
authors.lastname: Gao
authors.forename: Fengxuan
authors.initials: F
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Cui
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D008550:Melatonin; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D008550:Melatonin
keywords: Nox family; ischemia-reperfusion; ischemic stroke; melatonin; middle cerebral artery occlusion