Effect of shigatoxin-1 on arachidonic acid release by human glomerular epithelial cells.
Effect of shigatoxin-1 on arachidonic acid release by human glomerular epithelial cells.
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Shigatoxin-1 对人肾小球上皮细胞释放花生四烯酸的影响。
DOI：
10.1046/j.1523-1755.2001.0600031026.x
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发表时间：
2001
影响因子：
19.6
通讯作者：
Kohan,DE
中科院分区：
文献类型：
--
作者：
Schmid,DI;Kohan,DE
志贺毒素1对人肾小球上皮细胞释放花生四烯酸的影响。花生四烯酸（AA）代谢紊乱与溶血性尿毒症综合征（HUS）肾损伤的发病机制有关。然而，关于志贺毒素（Stx；溶血性尿毒综合征中假定的肾损害介质）对AA释放或肾细胞代谢的影响的信息很少。由于最近的研究表明肾小球上皮细胞（glomerular epithelial cells, GECs）可能是Stx的重要早期靶点，因此本研究旨在研究Stx对肾小球上皮细胞AA释放和代谢的影响。方法将培养的人GECs暴露于Stx1±脂多糖（LPS）中4 ~ 48小时，测定3h -花生四烯酸酯释放量、血栓素A2（TxA2）和前列腺环素（PGI2）的生成、环氧化酶（COX）活性，并分别测定磷脂酶A2（PLA2）和COX蛋白和mRNA水平。结果stx1增加了gec的花生四烯酸释放。单独LPS没有这种作用，但增加了Stx1的花生四烯酸释放。stx1刺激的花生四烯酸释放与cpla2、spla2蛋白和cPLA2mRNA水平升高相关。Stx1也增加了gec产生的txa2和pgi2；单独LPS不改变类二十烷酸的产生，但增强了Stx1效应。Stx1和LPS均刺激COX活性；然而，这些影响并不是相加的。虽然COX-1和COX-2 mRNA升高，但Stx1降低，LPS未改变COX1和COX2蛋白水平。结论stx1单用或联用LPS可增加人gec体内花生四烯酸酯的释放和类二十烷酸的产生；这种效应与pla2蛋白和mRNA水平升高有关。据我们所知，这是第一个确定stx1刺激AA释放机制的研究。这些结果表明，花生四烯酸酯的释放和代谢可能与溶血性尿毒综合征的肾损伤有关，也可能与其他肾细胞类型有关。
Effect of shigatoxin-1 on arachidonate release by human glomerular epithelial cells.BackgroundAltered arachidonic acid (AA) metabolism has been implicated in the pathogenesis of renal injury in the hemolytic uremic syndrome (HUS). However, there is very little information of the effect of shigatoxin (Stx; the putative mediator of renal damage in HUS) on AA release or metabolism by renal cells. Since recent studies have demonstrated that glomerular epithelial cells (GECs) may be important early targets of Stx, the current study was undertaken to examine the effects of Stx on AA release and metabolism by GECs.MethodsCultured human GECs were exposed to Stx1 ± lipopolysaccharide (LPS) for 4 to 48 hours followed by determination of3H-arachidonate release, thromboxane A2(TxA2) and prostacyclin (PGI2) production, cyclooxygenase (COX) activity, and Western and Northern analyses for phospholipase A2(PLA2) and COX protein and mRNA levels, respectively.ResultsStx1 increased arachidonate release by GECs. LPS alone had no such effect, but increased arachidonate release in response to Stx1. Stx1-stimulated arachidonate release correlated with elevations in cPLA2and sPLA2protein and cPLA2mRNA levels. Stx1 also increased both TxA2and PGI2production by GECs; LPS alone did not alter eicosanoid production, but augmented Stx1 effects. Both Stx1 and LPS stimulated COX activity; however, these effects were not additive. Although there was an accompanying elevation of COX-1 and COX-2 mRNA, Stx1 decreased and LPS did not change COX1 and COX2 protein levels.ConclusionsStx1 alone or in conjunction with LPS increases arachidonate release and eicosanoid production by human GECs; this effect correlates with increased PLA2protein and mRNA levels. To our knowledge, this is the first study identifying the mechanisms of Stx1-stimulated AA release. These results raise the possibility that arachidonate release and metabolism by GECs, and conceivably other renal cell types, are involved in renal injury in HUS.
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DOI：
10.1073/pnas.91.6.2280
发表时间：
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影响因子：
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作者：
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DOI：
--
发表时间：
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期刊：
Journal of lipid mediators
影响因子：
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作者：
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通讯作者：
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