ABCMdb

PMID: 10720936

Zeitlin PL
Pharmacologic restoration of delta F508 CFTR-mediated chloride current.
Kidney Int. 2000 Mar;57(3):832-7., [PubMed]

Sentences

No. Mutations Sentence Comment

62 ABCC7 p.Trp1282* (B) Class I mutations, such as W1282X, produce an early stop codon, unstable mRNA, and absence of CFTR protein. Login to comment 70 ABCC7 p.Gly551Asp G551D is a Class III mutation that is synthe- and Hsp90. Login to comment 72 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp The ability of gen- CFTR chloride channel activity at the cell surface in istein to activate G551D in the intestine of the G551D both immortalized human CF airway and biliary epithe- CF mouse has also been observed [40]. Login to comment 83 ABCC7 p.Trp1282* ABCC7 p.Arg553* W1282X and R553X Genistein, a member of the flavonoid class of mole- can be rescued in vitro. Login to comment 84 ABCC7 p.Trp1282* Given that W1282X mRNA is cules, activates CFTR through a highly debated mecha- unusually stable in certain patients [42], topical, inhaled, nism [34]. Login to comment 94 ABCC7 p.Gly551Asp G551D is a common ence response to isoproterenol [38]. Login to comment 98 ABCC7 p.Gly551Ser ABCC7 p.Gly1244Glu ABCC7 p.Gly1349Asp ABCC7 p.Ser1255Pro These mutants sus- ment of CF cells with 4-phenylbutyrate or low tempera- tain a reduced response to adenosine 5Ј-triphosphate ture to induce ⌬F508 trafficking to the plasma mem- (ATP); examples include S1255P, G551S, G1244E, and brane, allowed genistein to activate chloride transport G1349D. Login to comment 101 ABCC7 p.Arg117His ABCC7 p.Gly314Glu CF nasal epithelia alone or in combination with isoproterenol demonstrated a modest hyperpolarization in the CLASS IV CONDUCTION MUTATIONS AREnasal potential difference response to low chloride in ASSOCIATED WITH A MILD PHENOTYPEnormal volunteers, but not in CF patients homozygous Class IV mutants such as R117H, G314E, R334 W, andfor ⌬F508. Login to comment 102 ABCC7 p.Arg347Pro Restoration of ⌬F508 CFTR trafficking will R347P are associated with normal trafficking, proteinbe necessary for the flavonoids to be effective (abstract; kinase A (PKA)-dependent response to phosphoryla-Gondor et al, Pediatr Pulmon S17:253, 1998). Login to comment 104 ABCC7 p.Gly551Asp Defects instead lie in chlorideother hand, genistein alone induced a small chloride response in CF patients carrying one copy of the G551D conductance or channel gating (Fig. 1E). Login to comment 106 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Arg347Pro R347P affects the rate of chloride flow, Chemical and pharmacologic mediators of protein whereas R117H and P574H reduce the channel open trafficking are needed in CF and other diseases caused time. Login to comment 118 ABCC7 p.Arg117His A second murine model, Reprint requests to Pamela L. Zeitlin, M.D., The Johns Hopkins the R117H mouse, expresses a mutant which is found University, 600 N. Wolfe Street-Park 316, Baltimore, Maryland 21287- 2355, USA.on the cell surface in humans. Login to comment