| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print July 1, 2003
Surgery, University of California at San Francisco, San Francisco, CA 94110
Corresponding Author: mbh1{at}itsa.ucsf.edu
CFTR is expressed in epithelial cells and functions as a cAMP-regulated chloride channel. Although CFTR is expressed at high levels in the kidney, mutations in CFTR result in little or no apparent kidney dysfunction. In an effort to understand this phenomenon, we analyzed
J. Biol. Chem, 10.1074/jbc.M301924200
Submitted on February 24, 2003
Revised on June 4, 2003
Accepted on July 1, 2003
Mammalian osmolytes and S-nitrosoglutathione promote
F508 CFTR protein maturation and function
F508 CFTR maturation and function in kidney cells under conditions that are common to the kidney, namely osmotic stress. Kidney cells were grown in culture and adapted to 250 mM NaCl and 250 mM urea. HPLC analysis of lysates from kidney cells adapted to these conditions identified an increase in the cellular osmolytes glycerophosphoryl-choline, myo-inositol, sorbitol and taurine. In contrast to iso-osmotic conditions, hyperosmotic stress led to the proper folding and processing of F508 CFTR to its mature form. Furthermore, three of the cellular osmolytes when added individually to cells, proved effective in promoting the maturation and function of the F508 CFTR protein in both epithelial and fibroblast cells. Moreover, another small molecule, S-nitrosoglutathione (GSNO) is a substrate for gamma glutamyltranspeptidase, an abundant enzyme in the kidney, likewise promoted 508 CFTR maturation and function. GSNO-corrected F508 CFTR exhibited a shorter half-life as compared to wt CFTR. These results demonstrate the feasibility of a small molecule approach as a therapeutic treatment in promoting F508 CFTR maturation and function and indicate that an additional treatment maybe required to stabilize F508 CFTR protein once present at the plasma membrane. Finally, our observations may help to explain why F508 homozygous patients do not present with kidney dysfunction.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Bartoszewski, A. Rab, A. Jurkuvenaite, M. Mazur, J. Wakefield, J. F. Collawn, and Z. Bebok Activation of the Unfolded Protein Response by {Delta}F508 CFTR Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 448 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bartoszewski, A. Rab, G. Twitty, L. Stevenson, J. Fortenberry, A. Piotrowski, J. P. Dumanski, and Z. Bebok The Mechanism of Cystic Fibrosis Transmembrane Conductance Regulator Transcriptional Repression during the Unfolded Protein Response J. Biol. Chem., May 2, 2008; 283(18): 12154 - 12165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Zaman, S. Carraro, J. Doherty, E. M. Henderson, E. Lendermon, L. Liu, G. Verghese, M. Zigler, M. Ross, E. Park, et al. S-Nitrosylating Agents: A Novel Class of Compounds That Increase Cystic Fibrosis Transmembrane Conductance Regulator Expression and Maturation in Epithelial Cells Mol. Pharmacol., October 1, 2006; 70(4): 1435 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gaston, D. Singel, A. Doctor, and J. S. Stamler S-Nitrosothiol Signaling in Respiratory Biology Am. J. Respir. Crit. Care Med., June 1, 2006; 173(11): 1186 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Zaman, M. H. Hanigan, A. Smith, J. Vaughan, T. Macdonald, D. R. Jones, J. F. Hunt, and B. Gaston Endogenous S-Nitrosoglutathione Modifies 5-Lipoxygenase Expression in Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 387 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Yancey Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses J. Exp. Biol., August 1, 2005; 208(15): 2819 - 2830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bourgeois, M. J Coady, and J.-Y. Lapointe Determination of transport stoichiometry for two cation-coupled myo-inositol cotransporters: SMIT2 and HMIT J. Physiol., March 1, 2005; 563(2): 333 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. Fewell, C. M. Smith, M. A. Lyon, T. P. Dumitrescu, P. Wipf, B. W. Day, and J. L. Brodsky Small Molecule Modulators of Endogenous and Co-chaperone-stimulated Hsp70 ATPase Activity J. Biol. Chem., December 3, 2004; 279(49): 51131 - 51140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Clarke, L. R. Gawenis, T.-C. Hwang, N. M. Walker, D. B. Gruis, and E. M. Price A domain mimic increases {Delta}F508 CFTR trafficking and restores cAMP-stimulated anion secretion in cystic fibrosis epithelia Am J Physiol Cell Physiol, July 1, 2004; 287(1): C192 - C199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Griese, J. Ramakers, A. Krasselt, V. Starosta, S. van Koningsbruggen, R. Fischer, F. Ratjen, B. Mullinger, R. M. Huber, K. Maier, et al. Improvement of Alveolar Glutathione and Lung Function but Not Oxidative State in Cystic Fibrosis Am. J. Respir. Crit. Care Med., April 1, 2004; 169(7): 822 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Zhang, X.-T. Wang, H. Yue, S. W. Leung, P. H. Thibodeau, P. J. Thomas, and S. E. Guggino Organic Solutes Rescue the Functional Defect in {Delta}F508 Cystic Fibrosis Transmembrane Conductance Regulator J. Biol. Chem., December 19, 2003; 278(51): 51232 - 51242. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
