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LPS increases hepatic HIF-1alpha protein and expression of the HIF-1-dependent gene aldolase A in rats.

Authors: Scharte, M  Han, X  Uchiyama, T  Tawadrous, Z  Delude, RL  Fink, MP 
Citation: Scharte M, etal., J Surg Res. 2006 Oct;135(2):262-7. Epub 2006 Aug 23.
Pubmed: (View Article at PubMed) PMID:16930621
DOI: Full-text: DOI:10.1016/j.jss.2006.05.027

BACKGROUND: Cellular adaptation to hypoxia is mediated in part by the transcription factor hypoxia-inducible factor 1 (HIF-1). Accumulating data suggest that pro-inflammatory mediators can up-regulate HIF-1alpha protein expression and HIF-1 DNA-binding activity in the absence of hypoxia. Accordingly, we investigated HIF-1 mediated signaling in endotoxemic rats. MATERIALS AND METHODS: We studied three groups of male Sprague Dawley rats. Controls (N = 5) were injected i.p. with saline. Endotoxemic rats (N = 9) received a sublethal dose of lipopolysaccaride (Escherichia coli; 5 mg/kg, i.p.). A third group of rats (N = 5) received the HIF-1 stabilizing agent CoCl(2) (14 mg/kg, i.p.) at T = 0 h and T = 16 h. At T = 18 h, liver microvascular perfusion was measured using laser Doppler flowmetry and hepatic tissue samples were obtained. RNA was isolated and mRNA levels of the HIF-1 dependent genes aldolase A and vascular endothelial growth factor (VEGF) were determined using quantitative real-time RT-PCR. HIF-1alpha content was estimated by immunoprecipitation followed by Western blotting. RESULTS: HIF-1alpha increased in hepatic tissue after treatment with LPS or CoCl(2). LPS markedly increased hepatic expression of aldolase A, but failed to alter expression of VEGF. CoCl(2) increased aldolase A and VEGF mRNA expression. Although hepatic microvascular perfusion was comparable in saline- and LPS-treated rats, hepatic microvascular blood flow and aldolase A expression were significantly inversely correlated among endotoxemic rats (r = 0.773; P = 0.003). CONCLUSIONS: Increased expression of aldolase A in endotoxemic rats is mediated by both hypoxia-dependent and hypoxia-independent mechanisms.


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RGD Object Information
RGD ID: 1599054
Created: 2007-01-15
Species: All species
Last Modified: 2007-01-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.