HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 28, 19220-19232, July 14, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/28/19220    most recent M603100200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vila-Carriles, W. H. Articles by Benos, D. J. Search for Related Content PubMed PubMed Citation Articles by Vila-Carriles, W. H. Articles by Benos, D. J. Social Bookmarking                      What's this?

Surface Expression of ASIC2 Inhibits the Amiloride-sensitive Current and Migration of Glioma Cells^*

Wanda H. Vila-Carriles, Gergely Gy Kovacs, Biljana Jovov, Zhen-Hong Zhou, Amit K. Pahwa, Garrett Colby, Ogenna Esimai, G. Yancey Gillespie, Timothy B. Mapstone^¶, James M. Markert, Catherine M. Fuller, James K. Bubien, and Dale J. Benos¹

From the Departments of Physiology and Biophysics and Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 and the ^¶Department of Neurosurgery, University of Oklahoma, Health Sciences Center, Oklahoma City, Oklahoma 73104

Gliomas are primary brain tumors with a complex biology characterized by antigenic and genomic heterogeneity and a propensity for invasion into normal brain tissue. High grade glioma cells possess a voltage-independent, amiloride-inhibitable, inward Na⁺ current. This current does not exist in normal astrocytes or low grade tumor cells. Inhibition of this conductance decreases glioma growth and cell migration making it a potential therapeutic target. Our previous results have shown that the acid-sensing ion channels (ASICs), members of the epithelial Na⁺ channel (ENaC)/degenerin (DEG) family of ion channels are part of this current pathway. We hypothesized that one member of the ENaC/DEG family, ASIC2, is retained intracellularly and that it is the lack of functional expression of ASIC2 at the cell surface that results in hyperactivity of this conductance in high grade gliomas. In this study we show that the chemical chaperone, glycerol, and the transcriptional regulator, sodium 4-phenylbutyrate, inhibit the constitutively activated inward current and reduce cell growth and migration in glioblastoma multiforme. The results suggest that these compounds induce the movement of ASIC2 to the plasma membrane, and once there, the basally active inward current characteristic of glioma cells is abolished by inherent negative regulatory mechanisms. This in turn compromises the ability of the glioma cell to migrate and proliferate. These results support the hypothesis that the conductance pathway in high grade glioma cells is comprised of ENaC/DEG subunits and that abolishing this channel activity promotes a reversion of a high grade glioma cell to a phenotype resembling that of normal astrocytes.

Received for publication, March 31, 2006 , and in revised form, May 15, 2006.

^* This work was supported by National Institutes of Health Grants CA101952, DK37206, and P50 CA97247. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Physiology and Biophysics, The University of Alabama at Birmingham, 1918 University Blvd., MCLM 704, Birmingham, AL 35294-0005. Tel.: 205-934-6220; Fax: 205-934-2377; E-mail: benos{at}physiology.uab.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. C. Grifoni, S. E. McKey, and H. A. Drummond Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2022 - H2030. [Abstract] [Full Text] [PDF]

				C. M. Fuller and D. J. Benos Putting the brakes on vascular smooth muscle cell migration Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H1987 - H1988. [Full Text] [PDF]

				W. H. Vila-Carriles, Z.-H. Zhou, J. K. Bubien, C. M. Fuller, and D. J. Benos Participation of the Chaperone Hsc70 in the Trafficking and Functional Expression of ASIC2 in Glioma Cells J. Biol. Chem., November 23, 2007; 282(47): 34381 - 34391. [Abstract] [Full Text] [PDF]

				Z.-Y. Tan, Y. Lu, C. A. Whiteis, C. J. Benson, M. W. Chapleau, and F. M. Abboud Acid-Sensing Ion Channels Contribute to Transduction of Extracellular Acidosis in Rat Carotid Body Glomus Cells Circ. Res., November 9, 2007; 101(10): 1009 - 1019. [Abstract] [Full Text] [PDF]

				S. B. Ross, C. M. Fuller, J. K. Bubien, and D. J. Benos Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1181 - C1185. [Abstract] [Full Text] [PDF]

				R. H. Meltzer, N. Kapoor, Y. J. Qadri, S. J. Anderson, C. M. Fuller, and D. J. Benos Heteromeric Assembly of Acid-sensitive Ion Channel and Epithelial Sodium Channel Subunits J. Biol. Chem., August 31, 2007; 282(35): 25548 - 25559. [Abstract] [Full Text] [PDF]

				J.-H. Cho and C. C. Askwith Potentiation of acid-sensing ion channels by sulfhydryl compounds Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2161 - C2174. [Abstract] [Full Text] [PDF]