PMID- 15800052
OWN - NLM
STAT- MEDLINE
DCOM- 20050811
LR  - 20220225
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 289
IP  - 2
DP  - 2005 Aug
TI  - Changes in intracellular Ca2+ and pH in response to thapsigargin in human 
      glioblastoma cells and normal astrocytes.
PG  - C361-71
AB  - 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 Ca(2+) ([Ca(2+)](i)) and intracellular pH 
      (pH(i)) regulation could be involved in tumor formation. The sarco(endo)plasmic 
      reticulum Ca(2+)-ATPase (SERCA) is a major regulator of [Ca(2+)](i). We have 
      investigated the effect of inhibition of SERCA by thapsigargin (TG) on 
      [Ca(2+)](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 [Ca(2+)](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 
      [Ca(2+)](i) increase than in normal astrocytes. This increase was prevented in 
      nominally Ca(2+)-free buffer and by 2-APB, an inhibitor of store-operated Ca(2+) 
      channels. In addition, TG-activated Ca(2+) 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 Ca(2+) homeostasis and pH regulation in 
      tumor cells compared with normal human astrocytes.
FAU - Kovacs, Gergely Gy
AU  - Kovacs GG
AD  - Department of Physiology and Biophysics, University of Alabama at Birmingham, 
      Birmingham, AL 35294, USA.
FAU - Zsembery, Akos
AU  - Zsembery A
FAU - Anderson, Susan J
AU  - Anderson SJ
FAU - Komlosi, Peter
AU  - Komlosi P
FAU - Gillespie, G Yancey
AU  - Gillespie GY
FAU - Bell, P Darwin
AU  - Bell PD
FAU - Benos, Dale J
AU  - Benos DJ
FAU - Fuller, Catherine M
AU  - Fuller CM
LA  - eng
GR  - CA-101952/CA/NCI NIH HHS/United States
GR  - DK-3202/DK/NIDDK NIH HHS/United States
GR  - P50CA97247/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050330
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Calcium Channels)
RN  - 0 (Enzyme Inhibitors)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Astrocytes/drug effects/*metabolism
MH  - Calcium/*metabolism
MH  - Calcium Channels/drug effects/metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Glioblastoma/*metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration/drug effects
MH  - Intracellular Fluid/chemistry
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases
MH  - Thapsigargin/*pharmacology
EDAT- 2005/04/01 09:00
MHDA- 2005/08/12 09:00
CRDT- 2005/04/01 09:00
PHST- 2005/04/01 09:00 [pubmed]
PHST- 2005/08/12 09:00 [medline]
PHST- 2005/04/01 09:00 [entrez]
AID - 00280.2004 [pii]
AID - 10.1152/ajpcell.00280.2004 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2005 Aug;289(2):C361-71. doi: 
      10.1152/ajpcell.00280.2004. Epub 2005 Mar 30.