Distinct cellular pathways for resistance to urea stress and hypertonic stress.
Distinct cellular pathways for resistance to urea stress and hypertonic stress.
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抵抗尿素应激和高渗应激的独特细胞途径。
DOI：
10.1152/ajpcell.00150.2010
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kwon,HMoo
中科院分区：
文献类型：
--
作者：
Lee,SangDo;Choi,SooYoun;Kwon,HMoo
在使用升高的加压素进行抗利尿期间，尿素在肾髓质中积聚至非常高的浓度，造成相当大的细胞应激。局部细胞如何应对尿素应激与整个肾脏相关，因为肾髓质是肾干细胞的主要居住部位。先前的研究表明，肾细胞无法在中等尿素浓度下进行预处理以增强对尿素应激的抵抗力。相反，中度高盐度（中度高渗）预处理已被证明可以促进对尿素应激的抵抗力，这是由于分子伴侣热休克蛋白 70 (Hsp70) 的诱导，而分子伴侣热休克蛋白 70 (Hsp70) 由转录因子张力响应增强子结合蛋白 (TonEBP) 介导。在此，我们报告，在中等、无应激浓度的尿素预处理后，源自肾脏和成纤维细胞的细胞系表现出增强的对尿素应激的抵抗力。使用 TonEBP 敲除和免疫印迹分析，我们证明 TonEBP 和 Hsp70 对于增强尿素胁迫抵抗力是不可或缺的。这些数据表明肾髓质细胞能够通过激活不同的细胞途径来克服尿素应激。
During antidiuresis with elevated vasopressin, urea accumulates in the renal medulla to very high concentrations, imposing considerable cellular stress. How local cells cope with urea stress is relevant to the whole kidney because the renal medulla is the major site of residence for the renal stem cells. Previous studies showed that renal cells were incapable of preconditioning in moderate urea concentrations to enhance resistance to urea stress. Instead, preconditioning in moderately high salinity (moderate hypertonicity) has been shown to promote resistance to urea stress due to the induction of the molecular chaperone heat shock protein 70 (Hsp70), which is mediated by the transcription factor tonicity-responsive enhancer binding protein (TonEBP). Here we report that cell lines derived from the kidney and fibroblasts display enhanced resistance to urea stress after pretreatment in moderate, nonstressful concentrations of urea. Using TonEBP knockdown and immunoblot analyses, we demonstrate that TonEBP and Hsp70 are dispensable for the increased resistance to urea stress. These data suggest that cells in the renal medulla are capable of overcoming urea stress by activating distinct cellular pathways.