期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1772, 期 11-12, 页码 1199-1210出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2007.09.004
关键词
brain trauma; hydrogen peroxide; neuroprotection; oxidation; sodium selenite
This study was designed to investigate possible prevention of apoptotic cell death by selenium, an antioxidant, using cultured brain-derived neural progenitor cells (NPCs) and an experimental mouse brain trauma (BT) model. We tested some of the neuroprotective effects of sodium selenite in NPC cells by monitoring thioredoxin reductase (TR) expression, optimum H2O2 removal, and consequent inhibition of pro-apoptotic events including cytochrome c release and caspase 3 and 9 activation. Analysis of key apoptotic regulators during H2O2-induced apoptosis of NPCs showed that selenite blocks the activation of c-jun N-terminal protein kinase (JNK)/P38 mitogen-activated protein kinase (MAPK), and Akt survival protein. Moreover, selenite activates p44/42 MAPK and inhibits the downregulation of Bcl2 in selenite-treated NPC cells. For in vivo experiments, the effects of selenite on H2O2 neurotoxicity were tested using several biochemical and morphologic markers. Here we show that selenite potentially inhibits H2O2-induced apoptosis of NPCs and in traumatic brain injury. This in vivo protective function was also associated with inhibition of H2O2-induced reactive oxygen species (ROS) generation, cytochrome c release and caspase 3 and 9 activation. Our data show that the protective function of selenite through attenuation of secondary pathological events most likely results from its comprehensive effects that block apoptotic cell death, resulting in the maintenance of functional neurons and in inhibition of astrogliosis. The finding that selenite administration prevents secondary pathological events in an animal model of traumatic brain injury, as well as its efficacy, may provide novel drug targets for treating brain trauma. (c) 2007 Elsevier B.V. All rights reserved.
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