Linked Life Data

16135775

Source:http://linkedlifedata.com/resource/pubmed/id/16135775

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pubmed-article:16135775pubmed:abstractTextHypoxia evokes a common mechanism of oxygen sensing mediated by hypoxia-inducible transcription factors (HIF) in many mammalian cells. This study investigated the effect of hypoxia on group-IIA secretory phospholipase A(2) (sPLA(2)-IIA) expression in renal mesangial cells. Stimulation of cells with IL-1beta under normoxic conditions (21% O(2)) is known to induce expression and secretion of the group sPLA(2)-IIA. This induction is further enhanced by constantly reducing the O(2) concentration to 1% O(2), and is accompanied by increased sPLA(2) activity. To see whether hypoxia potentiates IL-1beta-induced sPLA(2)-IIA gene expression, a 2.67-kb fragment of the rat sPLA(2)-IIA promoter was fused to a luciferase reporter construct and used to transfect mesangial cells. Hypoxia alone is not able to activate the sPLA(2) promoter, whereas it significantly enhances IL-1beta-stimulated promoter activity. A deletion mutant of the promoter that lacks the two putative hypoxia responsive elements (HRE) is devoid of the potentiating effect of hypoxia. Moreover, site-directed mutagenesis of either of the two HRE is sufficient to abolish the potentiating effect of hypoxia. Electrophoretic mobility shift assays show that HIF-2alpha, which is the only HIF subtype expressed in mesangial cells, binds to both HRE in the sPLA(2)-IIA promoter. In summary, the data show that in an inflammatory setting hypoxia is able to potentiate sPLA(2)-IIA expression and activity in renal mesangial cells, and thereby may critically contribute to enhanced formation of inflammatory lipid mediators seen in a diverse range of kidney diseases.lld:pubmed
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pubmed-article:16135775pubmed:pagination2897-905lld:pubmed
pubmed-article:16135775pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:16135775pubmed:year2005lld:pubmed
pubmed-article:16135775pubmed:articleTitleHypoxia increases group IIA phospholipase A(2) expression under inflammatory conditions in rat renal mesangial cells.lld:pubmed
pubmed-article:16135775pubmed:affiliationPharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.lld:pubmed
pubmed-article:16135775pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16135775pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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