dtmrlogo dtmrlogo
homehomeresearchnewsdialogresourcesoutreachaboutuscontactus
RESEARCH
OUR SCIENTIFIC GOALS
CURRENT RESEARCH PROJECTS
SHARED TECHNICAL RESOURCES
ABSTRACTS AND TECHNICAL PAPERS

 

ABSTRACT: Arsenite Regulates Cystic Fibrosis Transmembrane Conductance Regulator and P-glycoprotein: Evidence of Pathway Independence

In the past, people have argued for and against the theory of reciprocal regulation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and P-glycoprotein (Pgp). Data have indicated that this may occur in vitro during drug-induced selection of cells, and in vivo during development. Much of this debate has been caused by a severe lack of mechanistic details involved in such regulation. Our past data indicate that certain Pgp modulators can affect CFTR expression and function. The goal of this study was to investigate the effects of trivalent arsenic
(arsenite), a known transcriptional activator of Pgp, on CFTR expression. In vitro analyses in T-84 cells that express basal levels of Pgp and CFTR were conducted using a variety of molecular techniques. Expressions of both genes were altered following treatment with arsenite in a dose- and time-dependent fashion. CFTR expression was suppressed almost three-fold by arsenite, along with a concomitant increase in P-glycoprotein expression. We also report that a member of the MAPK-family, the ERK-mediated signaling cascade is implicated in suppression of CFTR expression following treatment with arsenite. However, this particular pathway is not involved in regulation of P-glycoprotein expression in T-84 cells following treatment with arsenite. Thus, the regulatory pathways that control functional expression of CFTR and P-glycoprotein following arsenite treatment in T- 84 cells are distinct and independent.

 


Home | Toxic Metals | Research | News | Resources | Outreach | About Us | Contact Us | Site Map| Search

Dartmouth Home Page

Dartmouth Toxic Metals Research Program © 2001
This page was last modified on : Monday, 15-Jan-2007 11:33:23 EST

Web Administrator

Web design ©2001 Fairman Studios. All Rights Reserved.