自引率: 3%
被引量: 9355
通过率: 暂无数据
审稿周期: 3
版面费用: 暂无数据
国人发稿量: 1
投稿须知/期刊简介:
The Journal publishes the results of original research considered likely to further the physiological sciences in their broadest sense. Papers on pathophysiological or methodological topics will also be considered in so far as the information they contain can be used as a tool for further investigation of physiological mechanisms. In other words their subject matter must clearly convey a physiological message. Purely clinical papers will be excluded. Short communications are reserved for the publication of forefront material not yet in full paper form but of immediate interest to our readers. Articles should include a declaration to the effect that the experiments comply with the current laws of the country in which the experiments were performed.
期刊描述简介:
The Journal publishes the results of original research considered likely to further the physiological sciences in their broadest sense. Papers on pathophysiological or methodological topics will also be considered in so far as the information they contain can be used as a tool for further investigation of physiological mechanisms. In other words their subject matter must clearly convey a physiological message. Purely clinical papers will be excluded. Short communications are reserved for the publication of forefront material not yet in full paper form but of immediate interest to our readers. Articles should include a declaration to the effect that the experiments comply with the current laws of the country in which the experiments were performed.
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Attenuation of HIF-1 DNA-binding activity limits hypoxia-inducible endothelin-1 expression.
Hypoxia-inducible factors (HIFs) locate to HIF-binding sites (HBSs) within the hypoxia-response elements (HREs) of oxygen-regulated genes. Whereas HIF-1alpha is expressed ubiquitously, HIF-2alpha is found primarily in the endothelium, similar to endothelin-1 (ET-1) and fms-like tyrosine kinase 1 (Flt-1), the expression of which is controlled by HREs. We identified an unique sequence alteration in both ET-1 and Flt-1 HBSs not found in other HIF-1 target genes, implying that these HBSs might cause binding of HIF-2 rather than HIF-1. However, electrophoretic mobility shift assays showed HIF-1 and HIF-2 DNA complex formation with the unique ET-1 HBS to be about equal. Both DNA-binding and hypoxic activation of reporter genes using the ET-1 HBS was decreased compared with transferrin and erythropoietin HBSs. The Flt-1 HBS was non-functional when assayed in isolation, suggesting that additional factors are required for hypoxic up-regulation via the reported Flt-1 HRE. Interestingly, HIF-1 activity could be restored fully by point-mutating the ET-1 (but not the Flt-1) HBS, suggesting that the wild-type ET-1 HBS attenuated the full hypoxic response known from other oxygen-regulated genes. Such a mechanism might serve to limit the expression of this potent vasoconstrictor in hypoxia.
被引量：19 发表：2001
