ATP depletion of tubular cells causes dissociation of the zonula adherens and nuclear translocation of beta-catenin and LEF-1.
ATP depletion of tubular cells causes dissociation of the zonula adherens and nuclear translocation of beta-catenin and LEF-1.
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DOI：
10.1097/01.asn.0000012609.22035.44
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发表时间：
2002-05
期刊：
影响因子：
--
通讯作者：
V. Price;C. Reed;W. Lieberthal;J. Schwartz
中科院分区：
文献类型：
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作者：
V. Price;C. Reed;W. Lieberthal;J. Schwartz
本研究检测了与肾小管细胞ATP耗竭诱导的闭锁小带（ZA）结构和功能完整性可逆性破坏相关的事件。这表明，ATP耗竭后ZA的丢失与E-钙粘蛋白、α-连环蛋白和β-连环蛋白的撤回有关，可能是作为完整的钙粘蛋白-连环蛋白复合物从肾小管细胞的基底外侧膜中撤回。所有三种蛋白质的相对量在Triton X-100不溶性部分的细胞裂解物中增加，在Triton X-100可溶性池中减少。这些变化可随细胞ATP的补充而逆转。此外，ATP耗竭诱导β-连环蛋白和T细胞因子（TCF）/淋巴增强因子-1（LEF-1）（一种与β-连环蛋白相关的转录因子）的核转位。ZA蛋白作为完整的E-钙粘蛋白-连环蛋白复合物从质膜重新分布，促进了ZA在亚致死性缺血损伤后的快速恢复。β-catenin和TCF/LEF-1向细胞核的转位表明ATP耗竭可能激活wnt/wingless信号转导通路。因此，提供了全新的证据，即β-连环蛋白作为ZA的结构部分和作为wnt/wingless途径的组分的已知作用在肾小管细胞亚致死性缺血损伤后发挥作用。还推测β-连环蛋白和TCF/LEF-1的核转位调节缺血性损伤后的基因表达，并且可能有助于缺血性损伤后肾再生和修复所必需的事件。
This study examined the events associated with the reversible disruption of the structural and functional integrity of the zonula occludens (ZA) induced by ATP depletion of renal tubular cells. It shows that loss of the ZA after ATP depletion is associated with the withdrawal of E-cadherin, alpha-catenin, and beta-catenin, probably as intact cadherin-catenin complexes from the basolateral membrane of tubular cells. The relative amounts of all three proteins increased in the Triton X-100-insoluble fraction of cell lysates and decreased in the Triton X-100-soluble pool. These changes were reversed with repletion of cell ATP. It is additionally shown that ATP depletion induces nuclear translocation of beta-catenin and T cell factor (TCF)/lymphoid enhancer factor-1 (LEF-1), a transcriptional factor with which beta-catenin associates. The redistribution of the ZA proteins as intact E-cadherin-catenin complexes from the plasma membrane facilitates the rapid recovery of the ZA after sublethal ischemic injury. The translocation of beta-catenin and TCF/LEF-1 to the nucleus indicates that ATP depletion may activate the wnt/wingless signal transduction pathway. Thus, entirely novel evidence is provided that both of the known roles of beta-catenin, as a structural part of the ZA and as a component of the wnt/wingless pathway, play a role after sublethal ischemic injury to tubular cells. It is also speculated that the nuclear translocation of beta-catenin and TCF/LEF-1 modulates gene expression after ischemic injury and may contribute to events necessary for renal regeneration and repair after ischemic injury.