Zhang Zheng, Ferraris Joan D, Brooks Heddwen L, Brisc Ioana, Burg Maurice B
Laboratory of Kidney and Electrolyte Metabolism, National Heart Lung and Blood Institute, Bethesda, MD 20892, USA.
Am J Physiol Renal Physiol. 2003 Oct;285(4):F688-93. doi: 10.1152/ajprenal.00028.2003. Epub 2003 Jun 24.
TonEBP is a transcription factor that, when activated by hypertonicity, increases transcription of genes, including those involved in organic osmolyte accumulation. Surprisingly, it is expressed in virtually all tissues, including many never normally exposed to hypertonicity. We measured TonEBP mRNA (real-time PCR) and protein (Western blot analysis) in tissues of control (plasma osmolality 294 +/- 1 mosmol/kgH2O) and hyposmotic (dDAVP infusion plus water loading for 3 days, 241 +/- 2 mosmol/kgH2O) rats to test whether the ubiquitous expression of TonEBP mRNA is osmotically regulated around the normal plasma osmolality. TonEBP protein is reduced by hyposmolality in thymus and liver, but not in brain, and is not detected in heart and skeletal muscle. TonEBP mRNA decreases in brain and liver but is unchanged in other tissues. There are no general changes in mRNA of TonEBP-mediated genes: aldose reductase (AR) does not change in any tissue, betaine transporter (BGT1) decreases only in liver, taurine transporter (TauT) only in brain and thymus, and inositol transporter (SMIT) only in skeletal muscle and liver. Heat shock protein (Hsp)70-1 and Hsp70-2 mRNA increase greatly in most tissues, which cannot be attributed to decreased TonEBP activity. The conclusions are as follows: 1) TonEBP protein or mRNA expression is reduced by hyposmolality in thymus, liver, and brain. 2) TonEBP protein and mRNA expression are differentially regulated in some tissues. 3) Although AR, SMIT, BGT1, and TauT are regulated by TonEBP in renal medullary cells, other sources of regulation may predominate in other tissues. 4) TonEBP abundance and activity are regulated by factors other than tonicity in some tissues.
张力增强结合蛋白（TonEBP）是一种转录因子，当受到高渗激活时，它会增加基因的转录，包括那些参与有机渗透溶质蓄积的基因。令人惊讶的是，它几乎在所有组织中都有表达，包括许多正常情况下从未暴露于高渗环境的组织。我们检测了对照大鼠（血浆渗透压294±1毫摩尔/千克H₂O）和低渗大鼠（输注去氨加压素并饮水负荷3天，241±2毫摩尔/千克H₂O）组织中的TonEBP mRNA（实时定量PCR）和蛋白（蛋白质免疫印迹分析），以测试TonEBP mRNA在正常血浆渗透压附近是否受渗透压调节。低渗状态下，胸腺和肝脏中的TonEBP蛋白减少，但脑内未减少，且在心脏和骨骼肌中未检测到。脑和肝脏中的TonEBP mRNA减少，但其他组织中未改变。TonEBP介导的基因的mRNA没有普遍变化：醛糖还原酶（AR）在任何组织中都没有变化，甜菜碱转运体（BGT1）仅在肝脏中减少，牛磺酸转运体（TauT）仅在脑和胸腺中减少，肌醇转运体（SMIT）仅在骨骼肌和肝脏中减少。热休克蛋白（Hsp）70-1和Hsp70-2 mRNA在大多数组织中大幅增加，这不能归因于TonEBP活性降低。结论如下：1）低渗状态下，胸腺、肝脏和脑内的TonEBP蛋白或mRNA表达减少。2）TonEBP蛋白和mRNA表达在某些组织中受到不同调节。3）尽管AR、SMIT、BGT1和TauT在肾髓质细胞中受TonEBP调节，但在其他组织中可能以其他调节来源为主。4）在某些组织中，TonEBP的丰度和活性受渗透压以外的因素调节。
