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

This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/C361    most recent 00280.2004v1 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 ISI Web of Science 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 Kovacs, G. G. Articles by Fuller, C. M. Search for Related Content PubMed PubMed Citation Articles by Kovacs, G. G. Articles by Fuller, C. M.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Changes in intracellular Ca²⁺ and pH in response to thapsigargin in human glioblastoma cells and normal astrocytes

¹Department of Physiology and Biophysics, ²Nephrology Research and Training Center, Department of Medicine and ³Division of Neurosurgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and ⁴Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary

Submitted 11 June 2004 ; accepted in final form 22 March 2005

Despite extensive work in the field of glioblastoma research no significant increase in survival rates for this devastating disease has been achieved. It is known that disturbance of intracellular Ca²⁺ ([Ca²⁺]_i) and intracellular pH (pH_i) regulation could be involved in tumor formation. The sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) is a major regulator of [Ca²⁺]_i. We have investigated the effect of inhibition of SERCA by thapsigargin (TG) on [Ca²⁺]_i and pH_i in human primary glioblastoma multiforme (GBM) cells and GBM cell lines, compared with normal human astrocytes, using the fluorescent indicators fura-2 and BCECF, respectively. Basal [Ca²⁺]_i was higher in SK-MG-1 and U87 MG but not in human primary GBM cells compared with normal astrocytes. However, in tumor cells, TG evoked a much larger and faster [Ca²⁺]_i increase than in normal astrocytes. This increase was prevented in nominally Ca²⁺-free buffer and by 2-APB, an inhibitor of store-operated Ca²⁺ channels. In addition, TG-activated Ca²⁺ influx, which was sensitive to 2-APB, was higher in all tumor cell lines and primary GBM cells compared with normal astrocytes. The pH_i was also elevated in tumor cells compared with normal astrocytes. TG caused acidification of both normal and all GBM cells, but in the tumor cells, this acidification was followed by an amiloride- and 5-(N,N-hexamethylene)-amiloride-sensitive recovery, indicating involvement of a Na⁺/H⁺ exchanger. In summary, inhibition of SERCA function revealed a significant divergence in intracellular Ca²⁺ homeostasis and pH regulation in tumor cells compared with normal human astrocytes.

fura-2; BCECF; store-operated calcium channels

This article has been cited by other articles:

				S. Fedida-Metula, S. Elhyany, S. Tsory, S. Segal, M. Hershfinkel, I. Sekler, and D. Fishman Targeting lipid rafts inhibits protein kinase B by disrupting calcium homeostasis and attenuates malignant properties of melanoma cells Carcinogenesis, August 1, 2008; 29(8): 1546 - 1554. [Abstract] [Full Text] [PDF]