A5083092808- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Drug Transport and Resistance Mechanisms
- Neuroscience and Neuropharmacology Research
- Cardiac electrophysiology and arrhythmias
- Magnesium in Health and Disease
- Photoreceptor and optogenetics research
- Connexins and lens biology
- Parathyroid Disorders and Treatments
- Malaria Research and Control
- Neuroscience and Neural Engineering
- Electrolyte and hormonal disorders
- Electrochemical Analysis and Applications
- Neural dynamics and brain function
- Asthma and respiratory diseases
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Neurobiology and Insect Physiology Research
- Drug-Induced Hepatotoxicity and Protection
- Receptor Mechanisms and Signaling
- Analytical Chemistry and Sensors
- Mosquito-borne diseases and control
- Renal function and acid-base balance
Université Paris Cité
2012-2024
Inserm
2012-2024
Centre de Recherche des Cordeliers
2016-2024
Centre National de la Recherche Scientifique
2017-2024
Sorbonne Université
2017-2024
Metabolism and Renal Physiology
2018-2024
Sorbonne Paris Cité
2011-2019
Délégation Paris 5
2006-2018
Institut Necker Enfants Malades
1991-2003
Hôpital Necker-Enfants Malades
1978-1988
Epidemiologic studies suggest that genetic factors confer a predisposition to the formation of renal calcium stones or bone demineralization. Low serum phosphate concentrations due decrease in reabsorption have been reported some patients with these conditions, suggesting leading may contribute them. We hypothesized mutations gene coding for main sodium-phosphate cotransporter (NPT2a) be present disorders.We studied 20 urolithiasis demineralization and persistent idiopathic hypophosphatemia...
The extracellular Ca2+-sensing receptor (CaSR) plays an essential role in Ca2+ homeostasis by regulating the rate of parathyroid hormone (PTH) secretion and calcium reabsorption kidney. Activation renal CaSR is thought to inhibit paracellular divalent cation cortical ascending limb (cTAL) both directly indirectly via a decrease NaCl transport. However, patients with autosomal dominant hypocalcemia (ADH), caused gain-of-function mutations, defect tubular loss has not been described so far....
Impaired renal phosphate reabsorption, as measured by dividing the tubular maximal reabsorption of glomerular filtration rate (TmP/GFR), increases risks nephrolithiasis and bone demineralization. Data from animal models suggest that sodium-hydrogen exchanger regulatory factor 1 (NHERF1) controls transport. We sequenced NHERF1 gene in 158 patients, 94 whom had either or identified three distinct mutations seven patients with a low TmP/GFR value. No normal values mutations. The mutants...
Abstract Cystic fibrosis (CF) is caused by defective Fibrosis Transmembrane Conductance Regulator (CFTR) protein. Morbidity mainly due to early airway infection. We hypothesized that S. aureus clearance during the first hours of infection was impaired in CF human Airway Surface Liquid (ASL) because a lowered pH. The ASL pH bronchial epithelial cell lines and primary respiratory cells from healthy controls (WT) patients with measured microelectrode. antimicrobial capacity studied after apical...
The Slc26 gene family encodes several conserved anion transporters implicated in human genetic disorders, including Pendred syndrome, diastrophic dysplasia and congenital chloride diarrhea. We previously characterized the TAT1 (testis transporter 1; SLC26A8) protein specifically expressed male germ cells mature sperm showed that mouse, deletion of Tat1 caused sterility due to a lack motility, impaired capacitation structural defects flagella. Ca2+, Cl− HCO3− influxes trigger events required...
Renal ammonium (NH3 + NH4+) transport is a key process for body acid-base balance. It well known that several ionic systems allow NH4+ transmembrane translocation without high specificity NH4+, but it still debated whether NH3, and more generally, gas, may be transported by proteins. The human Rh glycoproteins have been proposed to mediate transport. Transport of and/or NH3 the epithelial C glycoprotein (RhCG) physiological importance in renal excretion because RhCG mainly expressed distal...
The functional properties and the pharmacological profile of recently cloned cDNA colonic P-ATPase α subunit (Crowson, M. S., Shull, G. E.(1992) J. Biol. Chem. 267, 13740-13748) were investigated by using Xenopus oocyte expression system. oocytes injected with cRNAs from Bufo marinus bladder or rat distal colon and/or β cRNA B. bladder. Two days after injection, K+ uptake was measured 86Rb+ as a surrogate, pH measurements performed means ion-selective microelectrodes. Co-injection lead to...
Proton secretion mediated by ATP12A protein on the surface of airway epithelium may contribute to cystic fibrosis (CF) lung disease favoring bacterial infection and obstruction. We studied in fresh bronchial samples cultured epithelial cells. In vivo, expression was found almost exclusively at apical side nonciliated cells submucosal glands, with much higher CF samples. This could be due inflammation, since treating supernatants or IL-4 (a cytokine that induces goblet cell hyperplasia)...
The most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, ΔF508, causes retention of ΔF508-CFTR endoplasmic reticulum and leads to absence CFTR Cl<sup>–</sup> channels plasma membrane. retains some channel activity so increased expression membrane can restore secretion deficiency. Recently, curcumin was shown rescue localization function. In our previous work, keratin 18 (K18) network implicated trafficking. Here, we hypothesized that could a functional...
Background The sodium-hydrogen exchanger regulatory factor 1 (NHERF1) binds to the main renal phosphate transporter NPT2a and parathyroid hormone (PTH) receptor. We have recently identified mutations in NHERF1 that decrease reabsorption by increasing PTH-induced cAMP production proximal tubule. Methods compared relevant parameters of homeostasis a patient with previously undescribed mutation control subjects. expressed mutant protein Xenopus Oocytes cultured cells study its effects on...
We previously have demonstrated that the colonic P-ATPase alpha subunit cDNA encodes an H,K-ATPase when expressed in Xenopus laevis oocytes. Besides its high level of amino acid homology (75%) with Na,K-ATPase, also shares a common pharmacological profile because both are ouabain-sensitive and Sch 28080-insensitive. These features raise possibility unrecognized property H, K-ATPase would be Na+ translocation. To test this hypothesis, ion-selective microelectrodes were used to measure...
Diffuse bronchiectasis is a common problem in respiratory clinics. We hypothesized that mutations the solute carrier 26A9 (SLC26A9) gene, encoding for chloride (Cl(-)) transporter mainly expressed lungs, may lead to defects mucociliary clearance. describe two missense variants SLC26A9 gene heterozygote patients presenting with diffuse idiopathic : p.Arg575Trp, identified patient also p.Phe508del CFTR gene; and p.Val486Ile. Expression of both mutants Xenopus laevis oocytes abolished...
Abstract Focal cortical dysplasia, hemimegalencephaly and tubers are paediatric epileptogenic malformations of development (MCDs) frequently pharmacoresistant mostly treated surgically by the resection epileptic cortex. Availability samples has allowed significant mechanistic discoveries directly from human material. Causal brain somatic or germline mutations in AKT/PI3K/DEPDC5/MTOR genes have been identified. GABAA-mediated paradoxical depolarization, related to altered chloride (Cl−)...
The human malaria parasite Plasmodium falciparum is capable of adapting to vastly different extracellular Ca(2+) environments while maintaining tight control its intracellular concentration. mechanisms underpinning homeostasis in this important pathogen are only partly understood. Here we have functionally expressed the putative Ca(2+)/H(+) antiporter PfCHA Xenopus laevis oocytes. Our data suggest that mediates H(+)-coupled and Mn(2+) exchange. apparent dissociation constant K(M) for 2.2 +/-...
A large body of genetic, reverse and epidemiological data has linked chloroquine-resistant malaria to polymorphisms within a gene termed pfcrt in the human malarial parasite Plasmodium falciparum. To investigate biological function chloroquine resistance transporter, PfCRT, as well its role resistance, we functionally expressed this protein Xenopus laevis oocytes. Our show that PfCRT-expressing oocytes exhibit depolarized resting membrane potential higher intracellular pH compared with...
Functional expression of the rat colonic H(+)-K(+)-ATPase was obtained by coexpressing its catalytic alpha-subunit and beta(1)-subunit Na(+)-K(+)-ATPase in Xenopus laevis oocytes. We observed that, oocytes expressing but not control (expressing beta(1) alone), NH(4)Cl induced a decrease (86)Rb uptake initial rate intracellular acidification extracellular enhanced, consistent with NH(+)(4) influx via H(+)-K(+)-ATPase. In absence K(+), only were able to acidify an medium supplemented NH(4)Cl....
The chloroquine resistance transporter of the human malaria parasite Plasmodium falciparum, PfCRT, is an important determinant to several quinoline and quinoline-like antimalarial drugs. PfCRT also plays essential role in physiology during development inside erythrocytes. However, function this besides its drug still unclear. Using electrophysiological flux experiments conducted on PfCRT-expressing Xenopus laevis oocytes, we show here that both wild-type a variant associated with transport...
The CFTR protein, encoded by the gene whose mutations induce Cystic Fibrosis, is an anion channel devoted mainly to chloride and bicarbonate transmembrane transport, but which also regulates transport of several other ions. Moreover, it implicated in cell response inflammation, and, reciprocally, cftr expression modulated inflammatory stimuli transduction pathways. Looking for a control ionic conditions, we investigated effect altered extracellular ion concentration on human pulmonary Calu-3...
BACKGROUND AND PURPOSE The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP‐dependent chloride channel in the plasma membrane of epithelia whose mutation cause genetic disease (CF). most frequent CFTR deletion Phe 508 and this mutant protein (delF508CFTR) does not readily translocate to rapidly degraded within cell. We hypothesized that treating epithelial cells with resveratrol, natural polyphenolic, phyto‐ooestrogenic compound from grapes, could modulate both expression...