The B1 H+-ATPase (Atp6v1b1) Subunit in Non–Type A Intercalated Cells is Required for Driving Pendrin Activity and the Renal Defense Against Alkalosis DOI
Soline Bourgeois,

Jana Kovacikova,

Milica Bugarski

et al.

Journal of the American Society of Nephrology, Journal Year: 2023, Volume and Issue: 35(1), P. 7 - 21

Published: Nov. 22, 2023

Significance Statement In the kidney, B1 H + -ATPase subunit is mostly expressed in intercalated cells (IC). Its importance acid-secreting type A ICs evident patients with inborn distal renal tubular acidosis and ATP6V1B1 mutations. However, protein also highly alkali-secreting non–type where its function incompletely understood. We demonstrate Atp6v1b1 knock out mice that critical for response to defend against alkalosis during an alkali load or chronic furosemide treatment. These findings highlight of maintaining acid–base balance metabolic challenges commonly used diuretics. Background Non–type collecting duct system express luminal Cl − /HCO 3 exchanger pendrin apical and/or basolateral -ATPases containing isoform. excrete bicarbonate alkalosis. Mutations (ATP6V1B1) cause due role acid secretory ICs. The has remained elusive. Methods examined responses −/− +/+ treatment furosemide. Results An 1 week resulted a more pronounced hypokalemic male ATP6v1b1 versus could not be compensated by respiration. Total expression activity ex vivo microperfused cortical ducts were reduced, β 2 -adrenergic stimulation was blunted mice. Basolateral strongly although B2 isoform increased. Ligation assays subunits indicated impaired assembly V 0 domains. During treatment, showed polyuria hyperchloremia . pendrin, water channel AQP2, epithelial sodium ENaC reduced. Conclusions Our data protecting reveal hitherto unrecognized need proper complexes ability stimulated.

Language: Английский

Natural Metal Polyphenol Nanozyme: Free Radical Scavenging and Antioxidation for the Treatment of Acute Kidney Injury DOI
Haitao Yuan, Fujing Wang, Zhen Wang

et al.

ACS Materials Letters, Journal Year: 2023, Volume and Issue: 5(10), P. 2807 - 2819

Published: Sept. 14, 2023

Acute kidney injury (AKI) is a severe renal dysfunction syndrome associated with high morbidity and mortality. Excessive production of reactive oxygen/nitrogen species (RONS) involved in the development progression AKI. Therefore, scavenging endogenous RONS reducing excessive oxidative stress essential for restoring function after Although nanozyme-mediated antioxidant therapy has been proposed as an effective strategy to prevent AKI, low uptake organ toxicity hinder its potential practical applications. To address this problem, we have designed metal-phenolic nanozyme named RosA-Mn NPs, which possesses cascade functionalities. The multienzymatic capacity well broad spectrum ROS free radical activities. As expected, NPs promote recovery mitochondrial reduce endoplasmic reticulum secondary inflammation through vitro. Moreover, overcome shortcomings artificial enzymes that failed rapidly accumulate tissues. tubular targeting could be exploited mitigate damage, improve functions, eventually Notably, also protect from oxidation cisplatin-induced AKI mouse model. RNA sequencing analysis demonstrated autophagy, apoptosis, antioxidation-related pathways were modulated by treatment NPs. In summary, activities biocompatibility show great other ROS-related diseases.

Language: Английский

Citations

28
Atypical Presentation of Distal Renal Tubular Acidosis in a Child: Correspondence DOI Creative Commons
Danqing Hu, Hanyan Meng, Wei Zhou

et al.

The Indian Journal of Pediatrics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Language: Английский

Citations

1
Urolithiasis unveiled: pathophysiology, stone dynamics, types, and inhibitory mechanisms: a review DOI Creative Commons

Essmat A. H. Allam

African Journal of Urology, Journal Year: 2024, Volume and Issue: 30(1)

Published: July 23, 2024

Abstract Urolithiasis is a multifaceted and common urological disorder characterized by the development of renal calculi. Calcium oxalate stones are most prevalent type calculi, forming when calcium combine to produce crystalline structures in urine. The incidence rates urolithiasis exhibit geographical variations, which determined factors such as geographic location, age, sex, dietary habits, genetics. increasing trend has emerged noteworthy public health issue, potentially attributed shifts lifestyle habits. In response this challenge, various inhibitors crystal formation, including small molecules, peptides, proteins, have been developed. Moreover, substances citrate, magnesium, inter-alpha-trypsin inhibitors, phytate, potassium, pyrophosphates show promise preventing kidney stones. A comprehensive metabolic assessment crucial, customized for each patient, effectively manage avoid recurrence urolithiasis. Although specific pharmacological treatments currently unavailable, some drugs can reduce pain. Some drugs, channel blockers like nifedipine, phosphodiesterase-5 tadalafil, alpha-blockers tamsulosin, thought lower ureteral contractions making smooth muscle relax. acute severe pain cases, intravenous administration narcotic analgesics anti-inflammatory agents may be employed emergency medical settings. To enhance therapeutic approaches, it essential gain more knowledge about pathophysiology targeting formation offers promising avenue prophylaxis. Identifying investigating potential lays framework creation effective targeted options. Graphical

Language: Английский

Citations

7
Transcytosis‐Based Renal Tubular Reabsorption of Luminescent Gold Nanoparticles for Enhanced Tumor Imaging DOI

Di Huang,

Yue Tan, Jiahao Tang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(11)

Published: Jan. 23, 2024

Abstract Transcytosis‐based tubular reabsorption of endogenous proteins is a well‐known energy‐saving pathway that prevents nutrient loss. However, utilization this for the delivery exogenous nanodrugs remains challenge. In study, using surface mimic strategy specific PEPT1/2‐targeted Gly−Sar peptide as ligand, renal‐clearable luminescent gold nanoparticles (P−AuNPs) were developed protein mimics to investigate transcytosis‐based substances. By regulating influential factors (H + content in lumens and PEPT1/2 transporter counts cells) Gly−Sar‐mediated transcytosis, efficient interaction between P−AuNPs renal cells was demonstrated both vitro vivo. Efficient transcellular transportation significantly guided back into bloodstream, which enhanced blood concentration bioavailability nanoparticles, contributing high‐contrast tumor imaging.

Language: Английский

Citations

5
Dmxl1 is an Essential Mammalian Gene that is Required for V-ATPase Assembly and Function In Vivo DOI Creative Commons
Amity F. Eaton, Elizabeth C. Danielson, Diane E. Capen

et al.

Function, Journal Year: 2024, Volume and Issue: 5(4)

Published: Jan. 1, 2024

Abstract The proton pumping V-ATPase drives essential biological processes, such as acidification of intracellular organelles. Critically, the domains, V1 and VO, must assemble to produce a functional holoenzyme. dysfunction results in cancer, neurodegeneration, diabetes, well systemic acidosis caused by reduced activity proton-secreting kidney intercalated cells (ICs). However, little is known about molecular regulation mammals. We identified novel interactor mammalian V-ATPase, Drosophila melanogaster X chromosomal gene-like 1 (Dmxl1), aka Rabconnectin-3A. yeast homologue Dmxl1, Rav1p, part complex that catalyzes reversible assembly domains. We, therefore,hypothesized Dmxl1 factor. Here, we generated IC-specific knockout (KO) mice, which had high urine pH, like B1 KO suggesting impaired function. Western blotting showed decreased expression (V1) a4 (VO) subunits were more less colocalized ICs. In parallel, subcellular fractionation revealed associated membrane fraction relative cytosol. Furthermore, proximity ligation assay performed using probes against also association. propose loss reduces holoenzyme assembly, thereby inhibiting may recruit domain facilitate with VO its absence be targeted for degradation. conclude bona fide

Language: Английский

Citations

4
Electrolyte disorders related emergencies in children DOI Creative Commons
Jakub Zieg, Shaarav Ghose, Rupesh Raina

et al.

BMC Nephrology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 30, 2024

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some the common serum abnormalities encountered clinical practice. Understanding pathophysiology, taking detailed history, performing physical examinations, ordering basic laboratory investigations are essential for timely proper management these conditions. We will discuss manifestations, diagnostic approaches, treatment strategies each disorder. aims to enhance approach patients with imbalance-related emergencies, ultimately improving patient outcomes.Trial registration manuscript does not include trial; instead, it an updated review literature.

Language: Английский

Citations

4
On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations DOI Creative Commons

Alexander Pushkin,

Liyo Kao, Hristina R. Zhekova

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 13, 2025

A transport protein's turnover rate (TOR) is the maximum of substrate translocation under saturating conditions. This parameter represents number transporting events per transporter molecule (assuming a single site) second (s). From this standpoint, transporter's TOR similar to an enzyme's catalytic constant. Knowledge allows comparison capacity various transporters at molecular level as well total cell and whole organ levels. Despite this, there currently very limited transporters, for which has been determined experimentally. In SLC4 family CO3 2-/HCO3 - erythrocyte AE1 (eAE1; SLC4A1) only member, (∼50,000 s-1). Whether other members have values unknown. Here we report measurements electrogenic Na+-CO3 2- cotransporter NBCe1-A (SLC4A4) kidney specific splice variant, kAE1, that play important roles in renal bicarbonate absorption are mutated proximal distal tubular acidosis respectively. We also remeasured eAE1 value comparison. had ∼30,400 s-1 whereas kAE1 significantly higher (62,000 60,500 respectively). modeled inward-facing (IF) conformation determine conformational changes during its cycle. Comparison IF model with our previously cryoelectron microscopy (cryoEM) outward-facing (OF) structure, demonstrates elevator-type mechanism small vertical ∼5 Å shift ion coordination site shown AE1. speculate movement plays role contributing high numbers transporters.

Language: Английский

Citations

0
Genetically predicted blood metabolites mediate the association between immune cell characteristics and urolithiasis: A Mendelian randomization study and mediation analysis DOI Creative Commons
Chengcheng Wei, Juan He, Jun Wen

et al.

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101547 - 101547

Published: Jan. 1, 2025

Language: Английский

Citations

0
Metabolic Acidosis DOI

Keiko I. Greenberg,

Stewart H. Lecker

Advances in Kidney Disease and Health, Journal Year: 2025, Volume and Issue: 32(1), P. 61 - 68

Published: Jan. 1, 2025

Language: Английский

Citations

0
Fanconi syndrome associated with pathological fractures of bilateral proximal femur and left femoral neck: A case report DOI Creative Commons

Qingping Lu,

Jin Zhang, Fuchun Yang

et al.

Asian Journal of Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0