Epigenetics of epithelial Na^+ channel-dependent sodium uptake and blood pressure regulation

查看全文 作　　者：Wenzheng [1,2]Zhang

机构地区：[1]Graduate School of Biomedical Sciences,the University of Texas Health Science Center at Houston;[2]Department of Internal Medicine,University of Texas Medical School at Houston

出　　处：《World Journal of Nephrology》索引2015年第4卷第3期,共4页

基　　金：Supported by National Institutes of Health Grant 2R01 DK080236 06A1 摘　　要：The epithelial Na+ channel(ENa C) consists of α,β,γsubunits.Its expression and function are regulated by aldosterone at multiple levels including transcription.ENa C plays a key role in Na+ homeostasis and blood pressure.Mutations in ENa C subunit genes result in hypertension or hypotension,depending on the nature of the mutations.Transcription of αENa C is considered as the rate-limiting step in the formation of functional ENa C.As an aldosterone target gene,αENa C is activated upon aldosterone-mineralocorticoid receptor binding to the cis-elements in the αENa C promoter,which is packed into chromatin.However,how aldosterone alters chromatin structure to induce changes in transcription is poorly understood.Studies by others and us suggest that Dot1a-Af9 complex represses αENa C by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENa C promoter.Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1 a and Af9 and by inducing Sgk1,which,in turn,phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction.MR attenuates Dot1aAf9 effect by competing with Dot1 a for binding Af9.Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1 a nuclear export.Af17-/-mice exhibit defects in ENa C expression,renal Na+ retention,and blood pressure control.This review gives a brief summary of these novel findings. 关键词：醛固酮高血压治疗方法临床分析

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Epigenetics of epithelial Na^+ channel-dependent sodium uptake and blood pressure regulation

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