In vivo expression profile of a H+-K+-ATPase α2-subunit promoter-reporter transgene

Zhang, Wenzheng; Xia, Xuefeng; Zou, Lei; Xu, Xiangyang; LeSage, Gene; Kone, Bruce C.

doi:10.1152/ajprenal.00043.2003

Cited by 15 publications

(9 citation statements)

References 26 publications

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“…The presence of HKA2 mRNA and protein has been confirmed in the connecting tubules (CNT), CCD, and OMCD by many studies in different species (32,48,85,90 ϩ depletion leads to the production of reactive oxygen species (ROS). These compounds activate different regulatory pathways, leading to phosphorylation of ROMK channels and inhibition of K ϩ secretion (for a review, see Ref.…”

Section: Relevance Of Hka2 In Renal Physiologymentioning

confidence: 94%

H-K-ATPase type 2: relevance for renal physiology and beyond

Crambert

2014

American Journal of Physiology-Renal Physiology

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H-K-ATPase type 2 (HKA2), also known as the “nongastric” or “colonic” H-K-ATPase, is broadly expressed, and its presence in the kidney has puzzled experts in the field of renal ion transport systems for many years. One of the most important and robust characteristics of this transporter is that it is strongly stimulated after dietary K+ restriction. This result prompted many investigators to propose that it should play a role in allowing the kidney to efficiently retain K+ under K+ depletion. However, the apparent absence of a clear renal phenotype in HKA2-null mice has led to the idea that this transporter is an epiphenomenon. This review summarizes past and recent findings regarding the functional, structural and physiological characteristics of H-K-ATPase type 2. The findings discussed in this review suggest that, as in the famous story, the ugly duckling of the X-K-ATPase family is actually a swan.

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Section: Relevance Of Hka2 In Renal Physiologymentioning

confidence: 94%

H-K-ATPase type 2: relevance for renal physiology and beyond

Crambert

2014

American Journal of Physiology-Renal Physiology

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“…Western blot analysis was performed according to our published protocols (13,38), with the exception of a modified cell lysis buffer (50 mM Tris, pH 7.4, 150 mM NaCl, 1 mM EDTA, pH 8.0, 1% Triton X-100, 1% SDS, and a cocktail of protease inhibitors) used to prepare whole cell lysates. Acid extracts abundant in free histones were prepared as described (36).…”

Section: Methodsmentioning

confidence: 99%

Aldosterone-sensitive repression of ENaCα transcription by a histone H3 lysine-79 methyltransferase

Zhang

Xia²,

Jalal

et al. 2006

American Journal of Physiology-Cell Physiology

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109

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Aldosterone is a major regulator of epithelial Na(+) absorption. One of its principal targets is the epithelial Na(+) channel alpha-subunit (ENaCalpha), principally expressed in the kidney collecting duct, lung, and colon. Models of aldosterone-mediated trans-activation of the ENaCalpha gene have focused primarily on interactions of liganded nuclear receptors with the ENaCalpha gene promoter. Herein, we demonstrate that the murine histone H3 lysine-79 methyltransferase, murine disruptor of telomeric silencing alternative splice variant "a" (mDot1a), is a novel component in the aldosterone signaling network controlling transcription of the ENaCalpha gene. Aldosterone downregulated mDot1a mRNA levels in murine inner medullary collecting ducts cells, which was associated with histone H3 K79 hypomethylation in bulk histones and at specific sites in the ENaCalpha 5'-flanking region, and trans-activation of ENaCalpha. Knockdown of mDot1a by RNA interference increased activity of a stably integrated ENaCalpha promoter-luciferase construct and expression of endogenous ENaCalpha mRNA. Conversely, overexpression of EGFP-tagged mDot1a resulted in hypermethylation of histone H3 K79 at the endogenous ENaCalpha promoter, repression of endogenous ENaCalpha mRNA expression, and decreased activity of the ENaCalpha promoter-luciferase construct. mDot1a-mediated histone H3 K79 hypermethylation and repression of ENaCalpha promoter activity was abolished by mDot1a mutations that eliminate its methyltransferase activity. Collectively, our data identify mDot1a as a novel aldosterone-regulated histone modification enzyme, and, through binding the ENaCalpha promoter and hypermethylating histone H3 K79 associated with the ENaCalpha promoter, a negative regulator of ENaCalpha transcription.

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“…IF was conducted as we reported before, 25,38 with the following modifications. Adobe Photoshop CS4 was used to examine the IF images and to score the staining of each primary antibody.…”

Section: If Studiesmentioning

confidence: 99%

Aqp2-Expressing Cells Give Rise to Renal Intercalated Cells

H¹,

Chen²,

Zhou

et al. 2013

Journal of the American Society of Nephrology

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The mammalian collecting duct comprises principal and intercalated cells, which maintain sodium/water and acid/base balance, respectively, but the epigenetic contributors to the differentiation of these cell types remain unknown. Here, we investigated whether the histone H3 K79 methyltransferase Dot1l, which is highly expressed in principal cells, participates in this process. Taking advantage of the distribution of aquaporin 2 (Aqp2), which localizes to principal cells of the collecting duct, we developed mice lacking Dot1l in Aqp2-expressing cells (Dot1l AC ) and found that these mice had approximately 20% fewer principal cells and 13%-16% more intercalated cells than control mice. This deletion of Dot1l in principal cells abolished histone H3 K79 methylation in these cells, but unexpectedly, most intercalated cells also had undetectable di-methyl K79, suggesting that Aqp2 + cells give rise to intercalated cells. These Aqp2 + cellderived intercalated cells were present in both developing and mature kidneys. Furthermore, compared with control mice, Dot1l AC mice had 40% higher urine volume and 18% lower urine osmolarity with relatively normal electrolyte and acid-base homeostasis. In conclusion, these data suggest that Dot1l deletion facilitates the differentiation of some a-and b-intercalated cells from Aqp2-expressing progenitor cells or mature principal cells.

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In vivo expression profile of a H⁺-K⁺-ATPase α₂-subunit promoter-reporter transgene

Cited by 15 publications

References 26 publications

H-K-ATPase type 2: relevance for renal physiology and beyond

H-K-ATPase type 2: relevance for renal physiology and beyond

Aldosterone-sensitive repression of ENaCα transcription by a histone H3 lysine-79 methyltransferase

Aqp2-Expressing Cells Give Rise to Renal Intercalated Cells

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