keyword
MENU ▼
Read by QxMD icon Read
search

Pseudohypoaldosteronism

keyword
https://www.readbyqxmd.com/read/28611771/tnf-lectin-like-domain-restores-epithelial-sodium-channel-function-in-frameshift-mutants-associated-with-pseudohypoaldosteronism-type-1b
#1
Anita Willam, Mohammed Aufy, Susan Tzotzos, Dina El-Malazi, Franziska Poser, Alina Wagner, Birgit Unterköfler, Didja Gurmani, David Martan, Shahid Muhammad Iqbal, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Istvan Czikora, Rudolf Lucas, Rosa Lemmens-Gruber, Waheed Shabbir
Previous in vitro studies have indicated that tumor necrosis factor (TNF) activates amiloride-sensitive epithelial sodium channel (ENaC) current through its lectin-like (TIP) domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide), showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individual ENaC subunits or ENaC carrying mutated glycosylation sites in the α-ENaC subunit were compared, revealing a similar mode of action for TNF and solnatide and corroborating the previous assumption that the lectin-like domain of TNF is the relevant molecular structure for ENaC activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28593901/pseudohypoaldosteronism-types-i-and-ii-little-more-than-a-name-in-common
#2
Dídac Casas-Alba, Jordi Vila Cots, Laura Monfort Carretero, Loreto Martorell Sampol, Maria-Christina Zennaro, Xavier Jeunemaitre, Juan Antonio Camacho Díaz
Pseudohypoaldosteronism (PHA) comprises a diverse group of rare diseases characterized by sodium and potassium imbalances incorrectly attributed to a defect in aldosterone production. Two different forms of PHA have been described, type I (PHAI) and type II (PHAII). PHAI has been subclassified into renal and systemic. Given the rarity and heterogeneity of this group of disorders we report three patients who carry PHA and a brief revision of current literature focused on the comparative analysis of PHAI and PHAII...
May 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28567665/severe-hyperkalemia-is-rescued-by-low-potassium-diet-in-renal-%C3%AE-enac-deficient-mice
#3
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard Claude Rossier, Edith Hummler
In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa(+)/LK(+)) diet. In the present study, we addressed whether renal βENaC expression is required for sodium and potassium balance or can be compensated by remaining (α and γ) ENaC subunits using adult nephron-specific knockout (Scnn1b(Pax8/LC1)) mice. Upon induction, these mice present a severe PHA-1 phenotype with weight loss, hyperkalemia, and dehydration, but unlike the Scnn1a(Pax8/LC1) mice without persistent salt wasting...
May 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28566208/development-of-wnk-signaling-inhibitors-as-a-new-class-of-antihypertensive-drugs
#4
Mari Ishigami-Yuasa, Yuko Watanabe, Takayasu Mori, Hiroyuki Masuno, Shinya Fujii, Eriko Kikuchi, Shinichi Uchida, Hiroyuki Kagechika
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia and hypertension despite a normal glomerular filtration rate. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK (STE20/SPS1-related proline/alanine-rich kinase) and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension. Thus, inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for a new class of antihypertensive drugs. In this study, we developed novel inhibitors of this signal cascade from the 9-aminoacridine lead compound 1, one of the hit compounds obtained by screening our chemical library for WNK-SPAK binding inhibitors...
July 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28557682/an-infant-presenting-with-failure-to-thrive-and-hyperkalaemia-owing-to-transient-pseudohypoaldosteronism-case-report
#5
Marieke De Clerck, Johan Vande Walle, Evelyn Dhont, Joke Dehoorne, Werner Keenswijk
A 3-month-old boy presented with failure to thrive and a history of a prenatally detected unilateral hydroureteronephrosis which was confirmed after birth. His growth and developmental milestones had been normal during the first 2 months but in the third month his appetite was poor with reduced intake but no vomiting. At presentation, his temperature was normal, there was mild dehydration and there was weight loss (his weight had decreased by 270 g in the past month). Haemoglobin was 11.9 g/dL, total white cell count 20...
May 30, 2017: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/28484659/systemic-pseudohypoaldosteronism-type-i-a-case-report-and-review-of-the-literature
#6
Nasifa Nur, Cameron Lang, Juanita K Hodax, Jose Bernardo Quintos
Systemic pseudohypoaldosteronism (PHA) type I is a rare genetic disorder resulting from mutations in the subunits of the epithelial sodium channel that manifests as severe salt wasting, hyperkalemia, and metabolic acidosis in infancy. In this article we report a patient with systemic PHA type I presenting with severe dehydration due to salt wasting at 6 days of life. She was found to have a known mutation in the SCNN1A gene and subsequently required treatment with sodium supplementation. We also review the clinical presentation, differential diagnosis, and treatment of systemic PHA type I and summarize data from 27 cases with follow-up data...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28414128/impaired-degradation-of-medullary-wnk4-in-the-kidneys-of-klhl2-knockout-mice
#7
Yuri Kasagi, Daiei Takahashi, Tomomi Aida, Hidenori Nishida, Naohiro Nomura, Moko Zeniya, Takayasu Mori, Emi Sasaki, Fumiaki Ando, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and Cullin3 (CUL3) genes were identified as being responsible for hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC cascade in the kidney's distal convoluted tubules (DCT)...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28409346/development-and-diseases-of-the-collecting-duct-system
#8
Lihe Chen, Paul J Higgins, Wenzheng Zhang
The collecting duct of the mammalian kidney is important for the regulation of extracellular volume, osmolarity, and pH. There are two major structurally and functionally distinct cell types: principal cells and intercalated cells. The former regulates Na(+) and water homeostasis, while the latter participates in acid-base homeostasis. In vivo lineage tracing using Cre recombinase or its derivatives such as CreGFP and CreER(T2) is a powerful new technique to identify stem/progenitor cells in their native environment and to decipher the origins of the tissue that they give rise to...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28365586/enac-and-romk-activity-are-inhibited-in-the-dct2-cnt-of-tgwnk4-phaii-mice
#9
Chengbiao Zhang, Lijun Wang, Xiao-Tong Su, Junhui Zhang, Dao-Hong Lin, Wen-Hui Wang
Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4(PHAII)) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na(+) delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na(+) channel (ENaC) and renal outer medullary K(+) channel (ROMK or Kir4.1) are expressed in the late DCT and play an important role in mediating K(+) secretion, the aim of the present study is to test whether ROMK and ENaC activity in the DCT/CNT are also compromised in the mice expressing PHAII mutant Wnk4...
April 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28348114/30-years-of-the-mineralocorticoid-receptor-mineralocorticoid-receptor-mutations
#10
REVIEW
Maria-Christina Zennaro, Fabio Fernandes-Rosa
Aldosterone and the mineralocorticoid receptor (MR) are key elements for maintaining fluid and electrolyte homeostasis as well as regulation of blood pressure. Loss-of-function mutations of the MR are responsible for renal pseudohypoaldosteronism type 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia and metabolic acidosis, despite extremely elevated levels of plasma renin and aldosterone...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28314693/wnk4-is-an-adipogenic-factor-and-its-deletion-reduces-diet-induced-obesity-in-mice
#11
Daiei Takahashi, Takayasu Mori, Eisei Sohara, Miyako Tanaka, Motoko Chiga, Yuichi Inoue, Naohiro Nomura, Moko Zeniya, Hiroki Ochi, Shu Takeda, Takayoshi Suganami, Tatemitsu Rai, Shinichi Uchida
The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. Although WNKs are widely expressed in the body, neither their metabolic functions nor their extrarenal role is clear. In this study, we found that WNK4 was expressed in mouse adipose tissue and 3T3-L1 adipocytes. In mouse primary preadipocytes and in 3T3-L1 adipocytes, WNK4 was markedly induced in the early phase of adipocyte differentiation. WNK4 expression preceded the expression of key transcriptional factors PPARγ and C/EBPα...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28286482/restoration-of-epithelial-sodium-channel-function-by-synthetic-peptides-in-pseudohypoaldosteronism-type-1b-mutants
#12
Anita Willam, Mohammed Aufy, Susan Tzotzos, Heinrich Evanzin, Sabine Chytracek, Sabrina Geppert, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Istvan Czikora, Rudolf Lucas, Rosa Lemmens-Gruber, Waheed Shabbir
The synthetically produced cyclic peptides solnatide (a.k.a. TIP or AP301) and its congener AP318, whose molecular structures mimic the lectin-like domain of human tumor necrosis factor (TNF), have been shown to activate the epithelial sodium channel (ENaC) in various cell- and animal-based studies. Loss-of-ENaC-function leads to a rare, life-threatening, salt-wasting syndrome, pseudohypoaldosteronism type 1B (PHA1B), which presents with failure to thrive, dehydration, low blood pressure, anorexia and vomiting; hyperkalemia, hyponatremia and metabolic acidosis suggest hypoaldosteronism, but plasma aldosterone and renin activity are high...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28249922/clinical-manifestation-and-molecular-analysis-of-three-korean-patients-with-the-renal-form-of-pseudohypoaldosteronism-type-1
#13
Hyo-Kyoung Nam, Myung-Hyun Nam, Hye Ryun Kim, Young-Jun Rhie, Kee Hwan Yoo, Kee-Hyoung Lee
Pseudohypoaldosteronism (PHA) type 1 is a rare, heterogeneous disease characterized by hyponatremia and hyperkalemia due to mineralocorticoid resistance. The clinical features of PHA are usually failure to thrive, vomiting, and dehydration in the neonatal period. Heterozygous mutations in the Nuclear receptor subfamily 3, group C, member 2 (NR3C2) gene result in the dominant renal form of PHA type 1. Mutations in the epithelial sodium channel gene result in the more severe, recessive, systemic form of PHA type 1...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28130590/expression-of-epithelial-sodium-channel-enac-and-cftr-in-the-human-epidermis-and-epidermal-appendages
#14
Israel Hanukoglu, Vijay R Boggula, Hananya Vaknine, Sachin Sharma, Thomas Kleyman, Aaron Hanukoglu
A major function of the skin is the regulation of body temperature by sweat secretions. Sweat glands secrete water and salt, especially NaCl. Excreted water evaporates, cooling the skin surface, and Na(+) ions are reabsorbed by the epithelial sodium channels (ENaC). Mutations in ENaC subunit genes lead to a severe multi-system (systemic) form of pseudohypoaldosteronism (PHA) type I, characterized by salt loss from aldosterone target organs, including sweat glands in the skin. In this study, we mapped the sites of localization of ENaC in the human skin by confocal microscopy using polyclonal antibodies generated against human αENaC...
January 27, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28052936/klhl3-knockout-mice-reveal-the-physiological-role-of-klhl3-and-the-pathophysiology-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#15
Emi Sasaki, Koichiro Susa, Takayasu Mori, Kiyoshi Isobe, Yuya Araki, Yuichi Inoue, Yuki Yoshizaki, Fumiaki Ando, Yutaro Mori, Shintaro Mandai, Moko Zeniya, Daiei Takahashi, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from the defective degradation of WNK1 and WNK4 by the KLHL3/CUL3 ubiquitin ligase complex. However, the other physiological in vivo roles of KLHL3 remain unclear. Therefore, here we generated KLHL3(-/-) mice that expressed β-galactosidase (β-Gal) under the control of the endogenous KLHL3 promoter...
April 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27900368/whole-exome-sequencing-reveals-an-inherited-r566x-mutation-of-the-epithelial-sodium-channel-%C3%AE-subunit-in-a-case-of-early-onset-phenotype-of-liddle-syndrome
#16
Linda M Polfus, Eric Boerwinkle, Richard A Gibbs, Ginger Metcalf, Donna Muzny, Narayanan Veeraraghavan, Megan Grove, Sanjay Shete, Stephanie Wallace, Dianna Milewicz, Neil Hanchard, James R Lupski, Syed Shahrukh Hashmi, Monesha Gupta-Malhotra
To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27882355/cullin-3-mutation-causes-arterial-stiffness-and-hypertension-through-a-vascular-smooth-muscle-mechanism
#17
Larry N Agbor, Stella-Rita C Ibeawuchi, Chunyan Hu, Jing Wu, Deborah R Davis, Henry L Keen, Frederick W Quelle, Curt D Sigmund
Cullin-3 (CUL3) mutations (CUL3Δ9) were previously identified in hypertensive patients with pseudohypoaldosteronism type-II (PHAII), but the mechanism causing hypertension and whether this is driven by renal tubular or extratubular mechanisms remains unknown. We report that selective expression of CUL3Δ9 in smooth muscle acts by interfering with expression and function of endogenous CUL3, resulting in impaired turnover of the CUL3 substrate RhoA, increased RhoA activity, and augmented RhoA/Rho kinase signaling...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27780983/a-novel-mutation-in-the-human-mineralocorticoid-receptor-gene-in-a-japanese-family-with-autosomal-dominant-pseudohypoaldosteronism-type-1
#18
Yoshimi Nishizaki, Makoto Hiura, Hidetoshi Sato, Yohei Ogawa, Akihiko Saitoh, Keisuke Nagasaki
No abstract text is available yet for this article.
October 2016: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
https://www.readbyqxmd.com/read/27780982/a-patient-with-pseudohypoaldosteronism-type-ii-complicated-by-congenital-hypopituitarism-carrying-a-klhl3-mutation
#19
Marie Mitani, Munehiro Furuichi, Satoshi Narumi, Tomonobu Hasegawa, Motoko Chiga, Shinichi Uchida, Seiji Sato
Pseudohypoaldosteronism type II (PHA II) is a renal tubular disease that causes hyperkalemia, hypertension, and metabolic acidosis. Mutations in four genes (WNK4, WNK1, KLHL3, and CUL3) are known to cause PHA II. We report a patient with PHA II carrying a KLHL3 mutation, who also had congenital hypopituitarism. The patient, a 3-yr-old boy, experienced loss of consciousness at age 10 mo. He exhibited growth failure, hypertension, hyperkalemia, and metabolic acidosis. We diagnosed him as having PHA II because he had low plasma renin activity with normal plasma aldosterone level and a low transtubular potassium gradient...
October 2016: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
https://www.readbyqxmd.com/read/27727489/phosphorylation-of-klhl3-at-serine-433-impairs-its-interaction-with-the-acidic-motif-of-wnk4-a-molecular-dynamics-study
#20
Lingyun Wang, Ji-Bin Peng
Interaction between the acidic motif (AM) of protein kinase WNK4 and the Kelch domain of KLHL3 are involved in the pathogenesis of pseudohypoaldosteronism type II, a hereditary form of hypertension. This interaction is disrupted by some disease-causing mutations in either WNK4 or KLHL3, or by angiotensin II- and insulin-induced phosphorylation of KLHL3 at serine 433, which is also a site frequently mutated in patients. However, the mechanism by which this phosphorylation disrupts the interaction is unclear...
February 2017: Protein Science: a Publication of the Protein Society
keyword
keyword
85263
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"