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KMID : 0381120060280040403
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Genes and Genomics
2006 Volume.28 No. 4 p.403 ~ p.412
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Involvement of Purα Gene in Neuroprotection Effects of Estrogen in Rat Ischemic Brain Model
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Yu Seong-Jin
Kim Ju-Ran
Lee Chae-Kwan
Kim Jeong-Ho
Kam Kyung-Yoon
Hong Jeong-Hwa
Kang Sung-Goo
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Abstract
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Stroke is a debilitating and prevalent disease in the world in which ischemic injury results from vascular occlusion in the brain. 17�� -estradiol valerate (E2) has been reported to exert neuroprotective effects when administered before an ischemic insult. Purine-rich element binding protein �� (Pur�� ), which is involved in diverse aspects of cellular function and also in neural regeneration, is strongly expressed in the neuronal cytoplasm. This study was conducted to evaluate the effects of E2 on brain injury and on the transcriptional level of Pur gene after transient focal ischemia in the rat brain. Focal cerebral ischemia was induced in rats by middle cerebral artery occlusion (MCAO). All animals underwent 1 h-ischemia, followed by 24 h-reperfusion. The brains were sliced coronally for staining with 2,3,5- triphenyltetrazolium chloride for measuring the ischemic area or subjected to total RNA extraction for the analysis of Pur�� gene expression. Histopathological analysis revealed that MCAO produced significant infarction in the cortex and striatum of the vehicle-treated group compared with the sham-operated group. In the E2-treated group, the infarct volume was decreased significantly in the both areas compared with the vehicle-treated group. The preventing effect of E2 on the brain damage was disappeared by treatment of ICI-182,780 (ICI), an E2 antagonist. The injury induced ischemia/reperfusion significantly decreased the levels of Pur�� gene expression in the ipsilateral cortex measured by RT-PCR and in situ hybridization P<0.05 vs. sham group). Interestingly, Pur�� gene expression was increased by E2 pre-treatment and this effect was partially antagonized by ICI cotreatment. This study, therefore, suggests that upregulation of Pur�� gene by E2 is partially involved in the action mechanisms for the neuroprotective effect of E2 in ischemic brain.
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KEYWORD
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17-estradiol valerate (E2), Ischemia, Purα, MCAO
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