keyword
https://read.qxmd.com/read/37634000/objective-and-subjective-measures-of-sleep-initiation-are-differentially-associated-with-dna-methylation-in-adolescents
#21
JOURNAL ARTICLE
Michael Larsen, Fan He, Yuka Imamura Kawasawa, Arthur Berg, Alexandros N Vgontzas, Duanping Liao, Edward O Bixler, Julio Fernandez-Mendoza
INTRODUCTION: The onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation...
August 26, 2023: Clinical Epigenetics
https://read.qxmd.com/read/37601283/maternal-taurine-as-a-modulator-of-cl-homeostasis-as-well-as-of-glycine-gaba-a-receptors-for-neocortical-development
#22
REVIEW
Tomonori Furukawa, Atsuo Fukuda
During brain and spinal cord development, GABA and glycine, the inhibitory neurotransmitters, cause depolarization instead of hyperpolarization in adults. Since glycine and GABAA receptors (GABAA Rs) are chloride (Cl- ) ion channel receptor, the conversion of GABA/glycine actions during development is influenced by changes in the transmembrane Cl- gradient, which is regulated by Cl- transporters, NKCC1 (absorption) and KCC2 (expulsion). In immature neurons, inhibitory neurotransmitters are released in a non-vesicular/non-synaptic manner, transitioning to vesicular/synaptic release as the neuron matures...
2023: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/37544354/wnk1-mediates-amphiregulin-induced-mmp9-expression-and-cell-invasion-in-human-extravillous-trophoblast-cells
#23
JOURNAL ARTICLE
Jung-Chien Cheng, Qingxue Meng, Qian Zhang, Lingling Zhang, Jiaye Chen, Tinglin Song, Lanlan Fang, Ying-Pu Sun
The invasion of human extravillous trophoblast (EVT) cells is a critical event required for a successful pregnancy. Amphiregulin, a ligand of the epidermal growth factor receptor (EGFR), has been shown to stimulate cell invasion in an immortalized human EVT cell line, HTR-8/SVneo. The with-no-lysine kinase 1 (WNK1) is involved in regulating cell invasion. It is known that WNK1 is expressed in the human placenta, but its role in human EVT cells remains unknown. In the present study, we show that AREG treatment phosphorylated WNK1 at Thr60 in both HTR-8/SVneo and primary human EVT cells...
August 4, 2023: Molecular and Cellular Endocrinology
https://read.qxmd.com/read/37383948/wnk1-enforces-macrophage-lineage-fidelity
#24
Alissa J Trzeciak, Waleska Saitz Rojas, Zong-Lin Liu, Adam S Krebs, Zhaoquan Wang, Pedro H V Saavedra, Isabella C Miranda, Allie Lipshutz, Jian Xie, Chou-Long Huang, Michael Overholtzer, Michael S Glickman, Christopher N Parkhurst, Thomas Vierbuchen, Christopher D Lucas, Justin S A Perry
UNLABELLED: The appropriate development of macrophages, the body's professional phagocyte, is essential for organismal development, especially in mammals. This dependence is exemplified by the observation that loss-of-function mutations in colony stimulating factor 1 receptor (CSF1R) results in multiple tissue abnormalities owing to an absence of macrophages. Despite this importance, little is known about the molecular and cell biological regulation of macrophage development. Here, we report the surprising finding that the chloride-sensing kinase With-no-lysine 1 (WNK1) is required for development of tissue-resident macrophages (TRMs)...
April 28, 2023: bioRxiv
https://read.qxmd.com/read/37307465/wnk1-controls-endosomal-trafficking-through-trim27-dependent-regulation-of-actin-assembly
#25
JOURNAL ARTICLE
Ji-Ung Jung, Melanie H Cobb
The protein kinase WNK1 (with-no-lysine 1) influences trafficking of ion and small-molecule transporters and other membrane proteins as well as actin polymerization state. We investigated the possibility that actions of WNK1 on both processes are related. Strikingly, we identified the E3 ligase tripartite motif-containing 27 (TRIM27) as a binding partner for WNK1. TRIM27 is involved in fine tuning the WASH (Wiskott-Aldrich syndrome protein and SCAR homologue) regulatory complex which regulates endosomal actin polymerization...
June 20, 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/37305581/indolyl-chalcone-derivatives-trigger-apoptosis-in-cisplatin-resistant-mesothelioma-cells-through-aberrant-tubulin-polymerization-and-deregulation-of-microtubule-associated-proteins
#26
JOURNAL ARTICLE
Sophia Steinlein, Frank Essmann, Amanda Franceschini Ghilardi, Heike Horn, Julia Schüler, Angelika Hausser, Lijun Sun, German Ott, Claudia Kalla
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a neoplasm with dismal prognosis and notorious resistance to the standard therapeutics cisplatin and pemetrexed. Chalcone derivatives are efficacious anti-cancer agents with minimal toxicity and have, therefore, gained pharmaceutical interest. Here, we investigated the efficacy of CIT-026 and CIT-223, two indolyl-chalcones (CITs), to inhibit growth and viability of MPM cells and defined the mechanism by which the compounds induce cell death...
2023: Frontiers in Oncology
https://read.qxmd.com/read/37241751/semisynthesis-biological-evaluation-and-molecular-docking-studies-of-barbatic-acid-derivatives-as-novel-diuretic-candidates
#27
JOURNAL ARTICLE
Xiang Yu, Yi Sui, Yinkai Xi, Yan Zhang, Guoyong Luo, Yi Long, Wude Yang
Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid ( 6a - q' ) were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 μmol/L in vitro. All target compounds were characterized using 1 H NMR, 13 C NMR, and HRMS, and the spatial structure of compound 6w was confirmed using X-ray crystallography. The biological results showed that some derivatives, including 6c , 6b' , and 6f' , exhibited potent diuretic activity, and 6j and 6m displayed promising litholytic activity...
May 10, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/37179366/membrane-tension-mediated-stiff-and-soft-tumor-subtypes-closely-associated-with-prognosis-for-prostate-cancer-patients
#28
JOURNAL ARTICLE
Dechao Feng, Jie Wang, Xu Shi, Dengxiong Li, Wuran Wei, Ping Han
BACKGROUND: Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. METHODS: Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages...
May 13, 2023: European Journal of Medical Research
https://read.qxmd.com/read/37079337/a-missense-mutation-of-the-wnk1-gene-affects-cold-tolerance-in-chinese-domestic-cattle
#29
JOURNAL ARTICLE
Xin Liu, Jialei Chen, Xinlong Xu, Jianyong Liu, Jicai Zhang, Haijian Cheng, Zulfiqar Ahmed, Bizhi Huang, Chuzhao Lei
Inclement weather conditions, especially cold stress, have threatened the cattle industry. Cattle exposed to cold environments for a longer time suffer developmental delay, immunity decline, and eventually death. WNK1 is a member of With-no-lysine kinases ( WNK s), widely expressed in animal organs and tissues. WNK1 and WNK4 are expressed in adipose tissue, and WNK4 promotes adipogenesis. WNK1 does not directly affect adipogenesis but has been shown to promote WNK4 expression in several tissues or organs. One missense mutation NC_037346...
April 20, 2023: Animal Biotechnology
https://read.qxmd.com/read/37071482/wnk1-promotes-water-homeostasis-by-acting-as-a-central-osmolality-sensor-for-arginine-vasopressin-release
#30
JOURNAL ARTICLE
Xin Jin, Jian Xie, Chia-Wei Yeh, Jen-Chi Chen, Chih-Jen Cheng, Cheng-Chang Lien, Chou-Long Huang
Maintaining internal osmolality constancy is essential for life. Release of arginine vasopressin (AVP) in response to hyperosmolality is critical. Current hypotheses for osmolality sensors in circumventricular organs (CVOs) of the brain focus on mechanosensitive membrane proteins. The present study demonstrated that intracellular protein kinase WNK1 was involved. Focusing on vascular-organ-of-lamina-terminalis (OVLT) nuclei, we showed that WNK1 kinase was activated by water restriction. Neuron-specific conditional KO (cKO) of Wnk1 caused polyuria with decreased urine osmolality that persisted in water restriction and blunted water restriction-induced AVP release...
June 1, 2023: Journal of Clinical Investigation
https://read.qxmd.com/read/37029785/the-wnk1-erk5-route-plays-a-pathophysiological-role-in-ovarian-cancer-and-limits-therapeutic-efficacy-of-trametinib
#31
JOURNAL ARTICLE
Adrián Sánchez-Fdez, Sofía Matilla-Almazán, Juan Carlos Montero, Sofía Del Carmen, Mar Abad, Sara García-Alonso, Somshuvra Bhattacharya, Kristin Calar, Pilar de la Puente, Alberto Ocaña, Atanasio Pandiella, Azucena Esparís-Ogando
BACKGROUND: The dismal prognosis of advanced ovarian cancer calls for the development of novel therapies to improve disease outcome. In this regard, we set out to discover new molecular entities and to assess the preclinical effectiveness of their targeting. METHODS: Cell lines, mice and human ovarian cancer samples were used. Proteome profiling of human phosphokinases, in silico genomic analyses, genetic (shRNA and CRISPR/Cas9) and pharmacological strategies as well as an ex vivo human preclinical model were performed...
April 2023: Clinical and Translational Medicine
https://read.qxmd.com/read/36970204/erratum-author-correction-to-tmem16a-inhibits-angiotensin-ii-induced-basilar-artery-smooth-muscle-cell-migration-in-a-wnk1-dependent-manner-acta-pharm-sin-b-11-12-2021-3994-4007
#32
Huaqing Zheng, Xiaolong Li, Xin Zeng, Chengcui Huang, Mingming Ma, Xiaofei Lv, Yajuan Zhang, Lu Sun, Guanlei Wang, Yanhua Du, Yongyuan Guan
[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].
March 2023: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/36941827/wnk1-a-molecular-crowding-sensor-links-phase-separation-to-cellular-physiological-stress
#33
JOURNAL ARTICLE
Tinghui Lan, Fangfang Zhou, Long Zhang
No abstract text is available yet for this article.
April 2023: MedComm
https://read.qxmd.com/read/36811882/the-impaired-wound-healing-process-is-a-major-factor-in-remodeling-of-the-corneal-epithelium-in-adult-and-adolescent-patients-with-keratoconus
#34
JOURNAL ARTICLE
Katarzyna Jaskiewicz, Magdalena Maleszka-Kurpiel, Eliza Matuszewska, Michal Kabza, Malgorzata Rydzanicz, Robert Malinowski, Rafal Ploski, Jan Matysiak, Marzena Gajecka
PURPOSE: Keratoconus (KTCN) is the most common corneal ectasia, characterized by pathological cone formation. Here, to provide an insight into the remodeling of the corneal epithelium (CE) during the course of the disease, we evaluated topographic regions of the CE of adult and adolescent patients with KTCN. METHODS: The CE samples from 17 adult and 6 adolescent patients with KTCN, and 5 control CE samples were obtained during the CXL and PRK procedures, respectively...
February 1, 2023: Investigative Ophthalmology & Visual Science
https://read.qxmd.com/read/36790288/control-of-sodium-and-potassium-homeostasis-by-renal-distal-convoluted-tubules
#35
JOURNAL ARTICLE
E A Gallafassi, M B Bezerra, N A Rebouças
Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron...
2023: Brazilian Journal of Medical and Biological Research
https://read.qxmd.com/read/36780970/cbx2-mediated-suppression-of-siah2-triggers-wnk1-accumulations-to-promote-glycolysis-in-hepatocellular-carcinoma
#36
JOURNAL ARTICLE
Zuoming Xu, Yinghong Wu, Meng Yang, Huamei Wei, Jian Pu
Previous studies have highlighted the poor prognosis of liver cancer, and treatment effects are overall limited. We aimed to confirm the biological roles of SIAH2 in liver cancer and provide potential therapeutic targets. Differential analysis was conducted based on public datasets and found that SIAH2 expressed lowly in HCC samples relative to normal tissues, which was demonstrated in tumor samples via immunohistochemistry (IHC). Besides, SIAH2 overexpression could significantly suppress HCC proliferation...
February 11, 2023: Experimental Cell Research
https://read.qxmd.com/read/36766805/lateral-diffusion-of-nkcc1-contributes-to-chloride-homeostasis-in-neurons-and-is-rapidly-regulated-by-the-wnk-signaling-pathway
#37
JOURNAL ARTICLE
Etienne Côme, Simon Blachier, Juliette Gouhier, Marion Russeau, Sabine Lévi
An upregulation of the Na+ -K+ -2Cl- cotransporter NKCC1, the main chloride importer in mature neurons, can lead to depolarizing/excitatory responses mediated by GABA type A receptors (GABAA Rs) and, thus, to hyperactivity. Understanding the regulatory mechanisms of NKCC1 would help prevent intra-neuronal chloride accumulation that occurs in pathologies with defective inhibition. The cell mechanisms regulating NKCC1 are poorly understood. Here, we report in mature hippocampal neurons that GABAergic activity controls the membrane diffusion and clustering of NKCC1 via the chloride-sensitive WNK lysine deficient protein kinase 1 (WNK1) and the downstream Ste20 Pro-line Asparagine Rich Kinase (SPAK) kinase that directly phosphorylates NKCC1 on key threonine residues...
January 31, 2023: Cells
https://read.qxmd.com/read/36733226/sevoflurane-induces-neurotoxic-effects-on-developing-neurons-through-the-wnk1-nkcc1-ca-2-drp-1-signalling-pathway
#38
JOURNAL ARTICLE
Ya-Fan Bai, Wen-Jing Li, Yu-Wei Ji, Li-Xin An, Li Zhang, Jun-Fa Li
Children repeatedly exposed to anaesthesia have a high risk of cognitive impairment, but the mechanism of its regulation in this context is unknown. The objective of this study was to investigate the possible toxic mechanism of sevoflurane through WNK1/NKCC1/Ca2+/Drp-1 signalling pathway. The hippocampal neuronal HT22 cell line was used in this study. The intervention group was treated with the WNK1 inhibitor WNK-463, CaN inhibitor FK506 and Drp-1 inhibitor Mdivi-1 respectively in the medium for 30 minutes before sevoflurane anaesthesia...
February 2, 2023: Clinical and Experimental Pharmacology & Physiology
https://read.qxmd.com/read/36712947/identification-of-a-class-of-wnk-isoform-specific-inhibitors-through-high-throughput-screening
#39
JOURNAL ARTICLE
Julita Chlebowicz, Radha Akella, John M Humphreys, Haixia He, Ashari R Kannangara, Shuguang Wei, Bruce Posner, Elizabeth J Goldsmith
INTRODUCTION: WNK [with no lysine (K)] kinases are serine/threonine kinases associated with familial hyperkalemic hypertension (FHHt). WNKs are therapeutic targets for blood pressure regulation, stroke and several cancers including triple negative breast cancer and glioblastoma. Here, we searched for and characterized novel WNK kinase inhibitors. METHODS: We used a ~210,000-compound library in a high-throughput screen, re-acquisition and assay, commercial specificity screens and crystallography to identify WNK-isoform-selective inhibitors...
2023: Drug Design, Development and Therapy
https://read.qxmd.com/read/36662229/b-cell-intrinsic-requirement-for-wnk1-kinase-in-antibody-responses-in-mice
#40
JOURNAL ARTICLE
Darryl A Hayward, Lesley Vanes, Stefanie Wissmann, Sujana Sivapatham, Harald Hartweger, Joshua Biggs O'May, Leonard L de Boer, Richard Mitter, Robert Köchl, Jens V Stein, Victor L J Tybulewicz
Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue, and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here, we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent and -independent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5, and CD40, and using intravital imaging, we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells...
March 6, 2023: Journal of Experimental Medicine
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