0 110

Cited 16 times in

Base Treatment Corrects Defects Due to Misfolding of Mutant Cystic Fibrosis Transmembrane Conductance Regulator

DC FieldValueLanguage
dc.contributor.author김경환-
dc.contributor.author이민구-
dc.date.accessioned2017-10-26T06:37:59Z-
dc.date.available2017-10-26T06:37:59Z-
dc.date.issued2005-
dc.identifier.issn0016-5085-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/151103-
dc.description.abstractBACKGROUND & AIMS: The most common form of the disease-causing cystic fibrosis transmembrane conductance regulator mutation, DeltaF508, leads to a misfolded protein that undergoes endoplasmic reticulum-associated degradation. Retrieval of misfolded protein from the cis-Golgi or pre-Golgi intermediate compartment is a critical factor in endoplasmic reticulum retention and degradation of DeltaF508 protein. Therefore, the inhibition of retrograde Golgi-to-endoplasmic reticulum traffic by the alkalinization of Golgi lumen may permit functional DeltaF508 protein to reach the cell surface. METHODS: Functional and biochemical effects of alkaline treatment on misfolded cystic fibrosis transmembrane conductance regulator-induced defects were measured in CFPAC-1 cells, which endogenously express DeltaF508 cystic fibrosis transmembrane conductance regulator, and in CHO cells, which heterologously express DeltaF508 cystic fibrosis transmembrane conductance regulator. The animal survival rate and the functional expression of cystic fibrosis transmembrane conductance regulator proteins were analyzed in homozygous DeltaF508 mice after chronic treatment with weak base NaHCO3. RESULTS: In CFPAC-1 and CHO cells, intracellular alkalization by reducing carbon dioxide concentrations in a carbon dioxide incubation chamber or intra-Golgi alkalization by bafilomycin A1 treatment increased the membrane expression of DeltaF508 protein and cystic fibrosis transmembrane conductance regulator-dependent anion transport. Notably, chronic administration of NaHCO3 increased the long-term survival of homozygous DeltaF508 mice and induced the functional expression of cystic fibrosis transmembrane conductance regulator in the luminal membrane of intestinal epithelium. CONCLUSIONS: We found that base treatments correct misfolded cystic fibrosis transmembrane conductance regulator-induced defects in vitro and in vivo. These results imply that the alkalization of intracellular compartments, in particular, Golgi or pre-Golgi intermediate compartments, can be a potential therapeutic target for the loss-of-function type of conformational diseases.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherW.B. Saunders-
dc.relation.isPartOfGASTROENTEROLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESH1-Methyl-3-isobutylxanthine/metabolism-
dc.subject.MESHAnimals-
dc.subject.MESHBicarbonates/metabolism-
dc.subject.MESHCell Line-
dc.subject.MESHChloride Channels/metabolism-
dc.subject.MESHChlorides/metabolism-
dc.subject.MESHColforsin/metabolism-
dc.subject.MESHColon/cytology-
dc.subject.MESHColon/metabolism-
dc.subject.MESHCricetinae-
dc.subject.MESHCyclic AMP/metabolism-
dc.subject.MESHCystic Fibrosis Transmembrane Conductance Regulator/chemistry*-
dc.subject.MESHCystic Fibrosis Transmembrane Conductance Regulator/genetics-
dc.subject.MESHCystic Fibrosis Transmembrane Conductance Regulator/metabolism*-
dc.subject.MESHDuodenum/cytology-
dc.subject.MESHDuodenum/metabolism-
dc.subject.MESHElectrophysiology-
dc.subject.MESHEndoplasmic Reticulum/metabolism-
dc.subject.MESHEnzyme Inhibitors/metabolism-
dc.subject.MESHGolgi Apparatus/metabolism*-
dc.subject.MESHHydrogen-Ion Concentration-
dc.subject.MESHIon Transport/physiology*-
dc.subject.MESHMacrolides/metabolism-
dc.subject.MESHMice-
dc.subject.MESHProtein Folding*-
dc.titleBase Treatment Corrects Defects Due to Misfolding of Mutant Cystic Fibrosis Transmembrane Conductance Regulator-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.googleauthorWan Namkung-
dc.contributor.googleauthorKyung Hwan Kim-
dc.contributor.googleauthorMin Goo Lee-
dc.identifier.doi10.1053/j.gastro.2005.08.049-
dc.contributor.localIdA00311-
dc.contributor.localIdA02781-
dc.relation.journalcodeJ00917-
dc.identifier.eissn1528-0012-
dc.identifier.pmid16344066-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0016508505017671-
dc.subject.keyword16344066-
dc.contributor.alternativeNameKim, Kyung Hwan-
dc.contributor.alternativeNameLee, Min Goo-
dc.citation.volume129-
dc.citation.number6-
dc.citation.startPage1979-
dc.citation.endPage1990-
dc.identifier.bibliographicCitationGASTROENTEROLOGY, Vol.129(6) : 1979-1990, 2005-
dc.date.modified2017-05-04-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.