CRCU

Chemical Research in Chinese Universities ›› 2009, Vol. 25 ›› Issue (4): 497-499.

• Letters • Previous Articles     Next Articles

Increased Sensitivity of Porcine ΔF508-CFTR Chloride Channel to Specific Small Molecule CFTR Inhibitors

ZHAO Hai-feng1, YU Ting2, LIU Xin1, LIU Rui1, ZHENG Lan1, SONG Li-na1, JIA Li1, YANG Hong3 and HE Cheng-yan1*   

  1. 1. Pepartment of Clinical Laboratory, China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China;
    2. The Second Hospital, Jilin University, Changchun 130021, P. R. China;
    3. Liaoning Provicial Key Laboratory of Biotechnolgy and Drug Discovery, School of Life Sciences, Liaoning Normal University, Dalian 116029, P. R. China
  • Received:2008-06-26 Revised:2008-07-21 Online:2009-07-25 Published:2009-10-16
  • Contact: HE Cheng-yan. E-mail: chengyanhe469@vip.sina.com
  • Supported by:

    Supported by the General Administration of Quality Supervision, Inspection and Quarantine of China(No.2006IK145), the Natural Science Foundation of Jilin Province, China(Nos.200705269 and 20030708), the Natural Science Foundation of Changchun City, China(No.2007sf19) and the Science and Technology Fund from the Education Department of Liaoning Province, China(No.20060492).

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Abstract:

Deletion of the codon encoding the phenylalanine residue at position 508(ΔF508) in the cystic fibrosis transmembrane conductance regulator(CFTR) is the most common mutation causing cystic fibrosis(CF). The human ΔF508 mutation results in a CFTR protein with impaired folding, trafficking, and gating in human and rodents. Recent studies suggest that pig ΔF508-CFTR can be efficiently processed to the plasma membrane as maturely glycosylated protein, indicating species difference of the molecular mechanisms of CFTR cellular maturation. In this study, the functional characterization in stably transfected FRT cells cultured at 37 °C demonstrates that pig ΔF508-CFTR is remarkably more sensitive to specific CFTR inhibitors CFTRinh-172 and GlyH101 than wildtype pig CFTR. The wildtype pig CFTR is more sensitive to GlyH101 than to CFTRinh-172. The present study indicates that the gating property of ΔF508-CFTR chloride channel is altered and GlyH101 may be a more suitable small molecule probe for generating CF phenotypes in pig tissues.

Key words: ΔF508-CFTR; Pig CFTR; Inhibitor; Cystic fibrosis