Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain

Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain
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DOI:
10.1152/jappl.1999.86.1.260
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发表时间:
1999-01-01
影响因子:
3.3
通讯作者:
LaManna, JC
LaManna, JC
中科院分区:
医学2区
文献类型:
--
作者:
Kuo, NT;Benhayon, D;LaManna, JC

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脑缺氧诱导脑血管功能的增加,可能是由血管内皮生长因子(VEGF)介导的,但目前尚不清楚是否需要VEGF来维持这种增加。在这些研究中,研究人员测量了在0.5 atm的低压舱中保存0、0.5、1、2、4、7和21天的成年小鼠脑VEGF mRNA和蛋白水平。缺氧伴VEGF mRNA表达短暂增加:0.5 d增加2倍,2 d最多增加5倍;随后在第4天减少,7-21天恢复到基础水平。缺氧诱导的VEGF蛋白表达呈双峰型,初期与VEGF mRNA表达平行。蛋白表达在12 h时开始小幅增加,在第2天达到最大值,在第4天短暂下降后,在第7天再次增加,21天后恢复到正常水平。因此,尽管持续缺氧,VEGF mRNA和蛋白水平在7天后恢复到基础水平。这些数据表明,在长时间缺氧的大脑中,VEGF表达存在代谢负反馈系统。
Brain hypoxia induces an increase in brain vascularity, presumably mediated by vascular endothelial growth factor (VEGF), but it is unclear whether VEGF is required to maintain the increase. In these studies, brain VEGF mRNA and protein levels were measured in adult mice kept in hypobaric chambers at 0.5 atm for 0, 0.5, 1, 2, 4, 7, and 21 days. Hypoxia was accompanied by a transient increase of VEGF mRNA expression: twofold by 0.5 day and a maximum of fivefold by 2 days; these were followed by a decrease at 4 days and a return to basal levels by 7-21 days. VEGF protein expression induced by hypoxia was bimodal, initially paralleling VEGF mRNA. There was an initial small increase at 12 h that reached a maximum by day 2, and, after a transient decrease on day 4, the protein expression increased again on day 7 before it returned to normoxic levels after 21 days. Thus, despite continued hypoxia, both VEGF mRNA and protein levels returned to basal after 7 days. These data suggest a metabolic negative-feedback system for VEGF expression during prolonged hypoxia in the brain.