Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :24043776
Publication Date : //

Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways.


The ability to maintain proper airway surface liquid (ASL) volume homeostasis is vital for mucus hydration and clearance, which are essential aspects of the mammalian lung's innate defense system. In cystic fibrosis (CF), one of the most common life-threatening genetic disorders, ASL dehydration leads to mucus accumulation and chronic infection. In normal airways, the secreted protein short palate lung and nasal epithelial clone 1 (SPLUNC1) effectively inhibits epithelial Na(+) channel (ENaC)-dependent Na(+) absorption and preserves ASL volume. In CF airways, it has been hypothesized that increased ENaC-dependent Na(+) absorption contributes to ASL depletion, and hence increased disease. However, this theory is controversial, and the mechanism for abnormal ENaC regulation in CF airways has remained elusive. Here, we show that SPLUNC1 is a pH-sensitive regulator of ENaC and is unable to inhibit ENaC in the acidic CF airway environment. Alkalinization of CF airway cultures prevented CF ASL hyperabsorption, and this effect was abolished when SPLUNC1 was stably knocked down. Accordingly, we resolved the crystal structure of SPLUNC1 to 2.8 Å. Notably, this structure revealed two pH-sensitive salt bridges that, when removed, rendered SPLUNC1 pH-insensitive and able to regulate ASL volume in acidic ASL. Thus, we conclude that ENaC hyperactivity is secondary to reduced CF ASL pH. Together, these data provide molecular insights into the mucosal dehydration associated with a range of pulmonary diseases, including CF, and suggest that future therapy be directed toward alkalinizing the pH of CF airways.

Authors : Garland Alaina L , Walton William G , Coakley Raymond D , Tan Chong D , Gilmore Rodney C , Hobbs Carey A , Tripathy Ashutosh , Clunes Lucy A , Bencharit Sompop , Stutts M Jackson , Betts Laurie , Redinbo Matthew R , Tarran Robert ,

Related products :

Catalog number Product name Quantity
20-783-73186 MOUSE ANTI HUMAN CFTR - CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN; CFTR; cAMP-dependent chloride channel; ATP-binding cassette transporter sub-family C member 7 Monoclonal 0.2 mg
EIAAB06989 ABCC7,ATP-binding cassette sub-family C member 7,cAMP-dependent chloride channel,CFTR,CFTR,Channel conductance-controlling ATPase,Cystic fibrosis transmembrane conductance regulator,Pig,Sus scrofa
EIAAB06988 Abcc7,ATP-binding cassette sub-family C member 7,cAMP-dependent chloride channel,CFTR,Cftr,Channel conductance-controlling ATPase,Cystic fibrosis transmembrane conductance regulator,Mouse,Mus musculus
EIAAB06991 ABCC7,ATP-binding cassette sub-family C member 7,Bos taurus,Bovine,cAMP-dependent chloride channel,CFTR,CFTR,Channel conductance-controlling ATPase,Cystic fibrosis transmembrane conductance regulator
EIAAB06992 Abcc7,ATP-binding cassette sub-family C member 7,cAMP-dependent chloride channel,CFTR,Cftr,Channel conductance-controlling ATPase,Cystic fibrosis transmembrane conductance regulator,Rat,Rattus norvegi
EIAAB06993 ABCC7,ATP-binding cassette sub-family C member 7,cAMP-dependent chloride channel,CFTR,CFTR,Channel conductance-controlling ATPase,Cystic fibrosis transmembrane conductance regulator,Oryctolagus cunicu
EIAAB06994 ABCC7,ATP-binding cassette sub-family C member 7,cAMP-dependent chloride channel,CFTR,CFTR,Channel conductance-controlling ATPase,Cystic fibrosis transmembrane conductance regulator,Homo sapiens,Human
40-2029-XX Cystic Fibrosis (various mutations) 10 nmoles
40-2029-XX Cystic Fibrosis (various mutations) 10nmoles
40-2029-10 Cystic Fibrosis Genemer (various mutations) 1Kit
BMMS-1249-MX Cystic Fibrosis Transmembrane Regulator (CFTR) MTO
BMMS-1249-X Cystic Fibrosis Transmembrane Regulator (CFTR) 0.2mL
BMMS-1248-B0 Cystic Fibrosis Transmembrane Regulator (CFTR) 0.1mL
40-2029-XX Cystic Fibrosis (various mutations); 10 nmols
BMMS-1248-B Cystic Fibrosis Transmembrane Regulator (CFTR) 1mL
BMMS-1248-MX Cystic Fibrosis Transmembrane Regulator (CFTR) MTO
40-2029-10 Cystic Fibrosis Genemer (various mutations) 10nmoles
BMMS-1248-X Cystic Fibrosis Transmembrane Regulator (CFTR) 0.2mL
BMMS-1249-B0 Cystic Fibrosis Transmembrane Regulator (CFTR) 0.1mL
BMMS-1249-B1 Cystic Fibrosis Transmembrane Regulator (CFTR) 0.5mL
BMMS-1249-B Cystic Fibrosis Transmembrane Regulator (CFTR) 1mL
CFP CFM1 Gene cystic fibrosis modifier 1
BMMS-1249-B1X Cystic Fibrosis Transmembrane Regulator (CFTR) 0.1mL
BMMS-1248-B1X Cystic Fibrosis Transmembrane Regulator (CFTR) 0.1mL
BMMS-1248-B1 Cystic Fibrosis Transmembrane Regulator (CFTR) 0.5mL


https://antibody-antibodies.com/ | https://gentaur.com/ | https://gen-script.com/ | https://diagenox.com/ | https://clonagen.com/ | http://gentaursearch.com/ | http://gentaurpub.com/ | https://gentaur-online.com/ | http://anti-anti-pdf.com/ | http://gentaur-worldwide.com/

 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur | Gentaur





GENTAUR Ltd.
Unicorn House, Station Cl
Hertfordshire, Potters Bar EN6 1TL
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017
RIB 30004 00187 00010092253 10
BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG
IBAN FR76 3000 4001 8700 0100 9225 310
france@gentaur.com | Gentaur | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: +49 0241 40 08 90 86, +49 0241 95 78 94 78, +49 0241 40 08 90 86
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur | Gentaur

RSS Feeds · Most Popular · Today's Favorites · All Time Favorites · Gentaur Policy
© Copyright 2010-2011 GENTAUR molecular products.