Source:http://linkedlifedata.com/resource/pubmed/id/16135775
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2005-9-26
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pubmed:abstractText |
Hypoxia 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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Group II Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/endothelial PAS domain-containing...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1046-6673
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2897-905
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16135775-Animals,
pubmed-meshheading:16135775-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:16135775-Cell Hypoxia,
pubmed-meshheading:16135775-Cells, Cultured,
pubmed-meshheading:16135775-Group II Phospholipases A2,
pubmed-meshheading:16135775-Inflammation,
pubmed-meshheading:16135775-Mesangial Cells,
pubmed-meshheading:16135775-Phospholipases A,
pubmed-meshheading:16135775-Rats,
pubmed-meshheading:16135775-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Hypoxia increases group IIA phospholipase A(2) expression under inflammatory conditions in rat renal mesangial cells.
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pubmed:affiliation |
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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