keyword
https://read.qxmd.com/read/37909881/hereditary-causes-of-hypertension-due-to-increased-sodium-transport
#1
JOURNAL ARTICLE
Jinwei Zhang
PURPOSE OF REVIEW: Hypertension, commonly known as high blood pressure, is a widespread health condition affecting a large number of individuals across the globe. Although lifestyle choices and environmental factors are known to have a significant impact on its development, there is growing recognition of the influence of genetic factors in the pathogenesis of hypertension. This review specifically focuses on the hereditary causes of hypertension that are associated with increased sodium transport through the thiazide-sensitive NaCl cotransporter (NCC) or amiloride-sensitive epithelial sodium channel (ENaC), crucial mechanisms involved in regulating blood pressure in the kidneys...
November 2, 2023: Current Opinion in Pediatrics
https://read.qxmd.com/read/37845702/insights-into-the-diverse-mechanisms-and-effects-of-variant-cul3-induced-familial-hyperkalemic-hypertension
#2
REVIEW
Prashant Sharma, Harish E Chatrathi
Familial hyperkalemic hypertension (FHHt), also known as Pseudohypoaldosteronism type II (PHAII) or Gordon syndrome is a rare Mendelian disease classically characterized by hyperkalemia, hyperchloremic metabolic acidosis, and high systolic blood pressure. The most severe form of the disease is caused by autosomal dominant variants in CUL3 (Cullin 3), a critical subunit of the multimeric CUL3-RING ubiquitin ligase complex. The recent identification of a novel FHHt disease variant of CUL3 revealed intricacies within the underlying disease mechanism...
October 16, 2023: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/37285722/identification-of-a-novel-klhl3-interacting-motif-in-the-c-terminal-region-of-wnk4
#3
JOURNAL ARTICLE
Lingyun Wang, Guojin Wu, Ji-Bin Peng
Mutations in with-no-lysine [K] kinase 4 (WNK4) and kelch-like 3 (KLHL3) are linked to pseudohypoaldosteronism type 2 (PHAII, also known as familial hyperkalemic hypertension or Gordon's syndrome). WNK4 is degraded by a ubiquitin E3 ligase with KLHL3 as the substrate adaptor for WNK4. Several PHAII-causing mutations, e.g. those in the acidic motif (AM) of WNK4 and in the Kelch domain of KLHL3, impair the binding between WNK4 and KLHL3. This results in a reduction in WNK4 degradation and an increase in WNK4 activity, leading to PHAII...
May 26, 2023: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/36303414/salt-losing-syndrome-in-a-girl-with-type-i-and-ii-pseudohypoaldosteronism
#4
JOURNAL ARTICLE
Agnieszka Szmigielska
BACKGROUND Pseudohypoaldosteronism (PHA) is characterized by renal tubular resistance to aldosterone and leads to hyponatremia, hyperkalemia, and metabolic acidosis. PHA is divided into 2 types: PHAI and PHAII. PHAI can be dominant (systemic disease) or recessive (renal form). PHAII causes hypertension with hyperkalemia and is recognized mostly in adults. PHA can be a life-threatening disease due to salt-wasting syndrome and severe hypovolemia. CASE REPORT We describe the case of a 2-month-old girl who was admitted to our hospital with hypovolemic shock due to salt-wasting syndrome...
October 28, 2022: American Journal of Case Reports
https://read.qxmd.com/read/36151370/wnk1-hsn2-mediates-neurite-outgrowth-and-differentiation-via-a-osr1-gsk3%C3%AE-lhx8-pathway
#5
JOURNAL ARTICLE
Masahiro Shimizu, Hiroshi Shibuya
With no lysine kinase 1 (WNK1) phosphorylates and activates STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress responsive kinase 1 (OSR1) to regulate ion homeostasis in the kidney. Mutations in WNK1 result in dysregulation of the WNK1-SPAK/OSR1 pathway and cause pseudohypoaldosteronism type II (PHAII), a form of hypertension. WNK1 is also involved in the autosomal recessive neuropathy, hereditary sensory and autonomic neuropathy type II (HSANII). Mutations in a neural-specific splice variant of WNK1 (HSN2) cause HSANII...
September 23, 2022: Scientific Reports
https://read.qxmd.com/read/36140271/the-post-translational-modification-networking-in-wnk-centric-hypertension-regulation-and-electrolyte-homeostasis
#6
REVIEW
Shiuan-Chen Lin, Chun Ma, Kao-Jung Chang, Han-Ping Cheong, Ming-Cheng Lee, Yuan-Tzu Lan, Chien-Ying Wang, Shih-Hwa Chiou, Teh-Ia Huo, Tsui-Kang Hsu, Ping-Hsing Tsai, Yi-Ping Yang
The with-no-lysine (WNK) kinase family, comprising four serine-threonine protein kinases (WNK1-4), were first linked to hypertension due to their mutations in association with pseudohypoaldosteronism type II (PHAII). WNK kinases regulate crucial blood pressure regulators, SPAK/OSR1, to mediate the post-translational modifications (PTMs) of their downstream ion channel substrates, such as sodium chloride co-transporter (NCC), epithelial sodium chloride (ENaC), renal outer medullary potassium channel (ROMK), and Na/K/2Cl co-transporters (NKCCs)...
September 2, 2022: Biomedicines
https://read.qxmd.com/read/35621709/generation-and-analysis-of-pseudohypoaldosteronism-type-ii-knock-in-mice-caused-by-a-nonsense-klhl3-mutation-in-the-kelch-domain
#7
JOURNAL ARTICLE
Chien-Ming Lin, Chih-Chien Sung, Sung-Sen Yang, Ying-Chuan Chen, Shih-Ming Huang, Shih-Hua Lin
Mutations in the Kelch-like 3 (KLHL3) gene are the most common cause of inherited pseudohypoaldosteronism type II (PHAII) featuring thiazide-sensitive hypertension and hyperkalemic metabolic acidosis. Although Klhl3R528H /+ knock-in (KI) mice carrying a missense mutation in the Kelch repeat domain have been reported, nonsense KLHL3 mutations in the same domain that cause PHAII have not been fully investigated in vivo. We generated and analyzed Klhl3 KI mice harboring a nonsense W523X mutation (corresponding to the human KLHL3 W470X mutation)...
June 2022: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/35442829/ubr5-is-a-novel-regulator-of-wnk1-stability
#8
JOURNAL ARTICLE
Ji-Ung Jung, Anwesha B Ghosh, Svetlana Earnest, Staci L Deaton, Melanie H Cobb
The with no lysine (K) 1 (WNK1) protein kinase maintains cellular ion homeostasis in many tissues through actions on ion cotransporters and channels. Increased accumulation of WNK1 protein leads to pseudohypoaldosteronism type II (PHAII), a form of familial hypertension. WNK1 can be degraded via its adaptor-dependent recruitment to the Cullin3-RBX1 E3 ligase complex by the ubiquitin-proteasome system. Disruption of this process also leads to disease. To determine if this is the primary mechanism of WNK1 turnover, we examined WNK1 protein stability and degradation by measuring its rate of decay after blockade of translation...
June 1, 2022: American Journal of Physiology. Cell Physiology
https://read.qxmd.com/read/34094823/regulatory-control-of-the-na-cl-co-transporter-ncc-and-its-therapeutic-potential-for-hypertension
#9
REVIEW
Nur Farah Meor Azlan, Maarten P Koeners, Jinwei Zhang
Hypertension is the largest risk factor for cardiovascular disease, the leading cause of mortality worldwide. As blood pressure regulation is influenced by multiple physiological systems, hypertension cannot be attributed to a single identifiable etiology. Three decades of research into Mendelian forms of hypertension implicated alterations in the renal tubular sodium handling, particularly the distal convoluted tubule (DCT)-native, thiazide-sensitive Na-Cl cotransporter (NCC). Altered functions of the NCC have shown to have profound effects on blood pressure regulation as illustrated by the over activation and inactivation of the NCC in Gordon's and Gitelman syndromes respectively...
May 2021: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/34022862/a-case-report-of-pseudohypoaldosteronism-type-ii-with-a-homozygous-klhl3-variant-accompanied-by-hyperthyroidism
#10
JOURNAL ARTICLE
Rui Zhang, Simin Zhang, Yingying Luo, Meng Li, Xin Wen, Xiaoling Cai, Xueyao Han, Linong Ji
BACKGROUND: Pseudohypoaldosteronism type II (PHAII), also called Gordon syndrome, is a rare hereditary disease caused by variants in the WNK1, WNK4, KLHL3 and CUL3 genes. The combination of PHAII with hyperthyroidism and secondary hyperparathyroidism has not been reported previously. CASE PRESENTATION: A 54-year-old female with recently diagnosed Graves' disease presented hyperkalemia, hypertension, hypercalciuria, elevated levels of parathyroid hormone (PTH) and normal renal function...
May 22, 2021: BMC Endocrine Disorders
https://read.qxmd.com/read/32286498/the-wnk-signaling-pathway-and-salt-sensitive-hypertension
#11
REVIEW
Taisuke Furusho, Shinichi Uchida, Eisei Sohara
The distal nephron of the kidney has a central role in sodium and fluid homeostasis, and disruption of this homeostasis due to mutations of with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), or Cullin 3 (CUL3) causes pseudohypoaldosteronism type II (PHAII), an inherited hypertensive disease. WNK1 and WNK4 activate the NaCl cotransporter (NCC) at the distal convoluted tubule through oxidative stress-responsive gene 1 (OSR1)/Ste20-related proline-alanine-rich kinase (SPAK), constituting the WNK-OSR1/SPAK-NCC phosphorylation cascade...
August 2020: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://read.qxmd.com/read/31371516/reply-to-farfel-et-al-is-enhanced-chloride-reabsorption-in-proximal-tubule-a-possible-mechanism-of-metabolic-acidosis-in-phaii
#12
JOURNAL ARTICLE
Jen-Chi Chen, Shih-Hua Lin, Chou-Long Huang, Chih-Jen Cheng
No abstract text is available yet for this article.
August 1, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31017050/investigating-specificity-of-the-anti-hypertensive-inhibitor-wnk463-against-with-no-lysine-kinase-family-isoforms-via-multiscale-simulations
#13
JOURNAL ARTICLE
Nisha A Jonniya, Parimal Kar
The With-No-Lysine (WNK) kinase family plays a significant role in regulating cation-chloride cotransporters, blood pressure and body fluid homeostasis. Mutations in the gene of WNK family, especially in WNK1 and WNK4 are responsible for pseudohypoaldosteronism type II (PHAII), characterized by hypertension. The selective inhibition of WNK1 over other isoforms has created an immense challenge in the design of an ATP competitive inhibitor due to their high conservatism. In this work, we have compared the selectivity of the inhibitor WNK463, which was designed for WNK1 with other WNK family isoforms by comprehensive molecular modeling, docking and molecular dynamics simulations in conjunction with the Molecular Mechanics Poisson-Boltzmann Surface Area method...
April 24, 2019: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/30931564/unveiling-the-distinct-mechanisms-by-which-disease-causing-mutations-in-the-kelch-domain-of-klhl3-disrupt-the-interaction-with-the-acidic-motif-of-wnk4-through-molecular-dynamics-simulation
#14
JOURNAL ARTICLE
Lingyun Wang, Chen Jiang, Ruiqi Cai, Xing-Zhen Chen, Ji-Bin Peng
Kelch-like 3 (KLHL3) is a substrate adaptor of an E3 ubiquitin ligase complex that regulates the degradation of its substrates, including with-no-lysine [K] kinase 4 (WNK4). Mutations in KLHL3 are associated with pseudohypoaldosteronism type II (PHAII), a hereditary form of hypertension. Many PHAII-causing mutations are located in the Kelch domain of KLHL3 that binds with WNK4; however, detailed mechanisms by which these mutations disrupt the binding are not well understood. In the present study we use molecular dynamics simulations and western blot analyses to examine the effects of these mutations on the interaction between the Kelch domain of KLHL3 and the acidic motif (AM) of WNK4...
April 1, 2019: Biochemistry
https://read.qxmd.com/read/30765526/wnk4-kinase-is-a-physiological-intracellular-chloride-sensor
#15
JOURNAL ARTICLE
Jen-Chi Chen, Yi-Fen Lo, Ya-Wen Lin, Shih-Hua Lin, Chou-Long Huang, Chih-Jen Cheng
With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl- ) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. The mechanism is thought to be important for physiological regulation of NCC by extracellular potassium...
March 5, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30148674/generation-and-analysis-of-a-mouse-model-of-pseudohypoaldosteronism-type-ii-caused-by-klhl3-mutation-in-btb-domain
#16
JOURNAL ARTICLE
Chien-Ming Lin, Chih-Jen Cheng, Sung-Sen Yang, Min-Hua Tseng, Ming-Tso Yen, Chih-Chien Sung, Shih-Hua Lin
The Kelch-like 3 ( KLHL3) mutations contributed to the most common causative genes in patients with pseudohypoaldosteronism type II (PHAII); however, the molecular mechanisms of PHAII-causing mutations in BTB domain of KLHL3 in vivo have not been investigated. We generated and analyzed Klhl3 knock-in (KI) mice carrying a missense M131V mutation in the BTB domain (corresponding to human KLHL3 M78V mutation). Klhl3M131V/+ KI mice exhibited typical PHAII phenotype with an exaggerated diuretic response to hydrochlorothiazide...
August 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30146013/a-mouse-model-of-pseudohypoaldosteronism-type-ii-reveals-a-novel-mechanism-of-renal-tubular-acidosis
#17
JOURNAL ARTICLE
Karen I López-Cayuqueo, Maria Chavez-Canales, Alexia Pillot, Pascal Houillier, Maximilien Jayat, Jennifer Baraka-Vidot, Francesco Trepiccione, Véronique Baudrie, Cara Büsst, Christelle Soukaseum, Yusuke Kumai, Xavier Jeunemaître, Juliette Hadchouel, Dominique Eladari, Régine Chambrey
Pseudohypoaldosteronism type II (PHAII) is a genetic disease characterized by association of hyperkalemia, hyperchloremic metabolic acidosis, hypertension, low renin, and high sensitivity to thiazide diuretics. It is caused by mutations in the WNK1, WNK4, KLHL3 or CUL3 gene. There is strong evidence that excessive sodium chloride reabsorption by the sodium chloride cotransporter NCC in the distal convoluted tubule is involved. WNK4 is expressed not only in distal convoluted tubule cells but also in β-intercalated cells of the cortical collecting duct...
September 2018: Kidney International
https://read.qxmd.com/read/29869755/decreased-klhl3-expression-is-involved-in-the-pathogenesis-of-pseudohypoaldosteronism-type-ii-caused-by-cullin-3-mutation-in-vivo
#18
JOURNAL ARTICLE
Sayaka Yoshida, Yuya Araki, Takayasu Mori, Emi Sasaki, Yuri Kasagi, Kiyoshi Isobe, Koichiro Susa, Yuichi Inoue, Pascale Bomont, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
BACKGROUND: Pseudohypoaldosteronism type II (PHAII) is a hereditary hypertensive disease caused by mutations in four genes: WNK1, WNK4, Kelch-like3 (KLHL3), and cullin3 (CUL3). Recently, it was revealed that CUL3-KLHL3 E3 ligase complex ubiquitinates WNK1 and WNK4, leading to their degradation, and that a common pathogenesis of PHAII is defective WNK degradation due to CUL3-KLHL3 E3 ligase complex impairment. PHAII-causing CUL3 mutations mediate exon9 skipping, producing a CUL3 protein with a 57-amino acid deletion (Δ403-459)...
December 2018: Clinical and Experimental Nephrology
https://read.qxmd.com/read/29511623/a-novel-mutation-in-exon-9-of-cullin-3-gene-contributes-to-aberrant-splicing-in-pseudohypoaldosteronism-type-ii
#19
JOURNAL ARTICLE
Leping Shao, Li Cui, Jingru Lu, Yanhua Lang, Irene Bottillo, Xiangzhong Zhao
Pseudohypoaldosteronism type II (PHAII) is a rare renal tubular disease that is inherited in an autosomal dominant manner. Mutations in four genes ( WNK1 , WNK4 , CUL3, and KLHL3 ) have been identified to be responsible for this disease. Cullin 3 (CUL3) and KLHL3 are subunits of Cullin-RING E3 ubiquitin ligase complexes, and the serine-threonine kinases WNK1 and WNK4 are substrates of this ubiquitin ligase. For CUL3 , all mutations associated with PHAII exclusively lead to exon 9 skipping. In this study, we identified a Chinese PHAII kindred caused by a novel synonymous mutation (c...
March 2018: FEBS Open Bio
https://read.qxmd.com/read/28743496/wnk4-is-indispensable-for-the-pathogenesis-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#20
JOURNAL ARTICLE
Koichiro Susa, Eisei Sohara, Daiei Takahashi, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida
WNK-OSR1/SPAK-NCC signaling cascade is important for regulating salt balance and blood pressure. Activation of WNK-OSR1/SPAK-NaCl cotransporter (NCC) cascade increases sodium reabsorption in the kidney, leading to pseudohypoaldosteronism type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. It has been previously demonstrated that the amount of phosphorylated and total NCC markedly decreased in WNK4-/- mice, indicating that WNK4 plays a major role for activation of OSR1/SPAK-NCC signaling...
September 23, 2017: Biochemical and Biophysical Research Communications
keyword
keyword
67923
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

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"

We want to hear from doctors like you!

Take a second to answer a survey question.