PMID- 15794938
OWN - NLM
STAT- MEDLINE
DCOM- 20050511
LR  - 20151119
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 69
IP  - 8
DP  - 2005 Apr 15
TI  - 2-Aminoethoxydiphenyl borate perturbs hormone-sensitive calcium stores and blocks 
      store-operated calcium influx pathways independent of cytoskeletal disruption in 
      human A549 lung cancer cells.
PG  - 1177-86
AB  - Recent studies have identified novel actions for 2-aminoethoxydiphenyl borate 
      (2-APB) in triggering calcium release and enhancing calcium influx induced by the 
      depletion of intracellular calcium stores. In this study, we have examined the 
      effects of 2-APB on the human lung adenocarcinoma A549 cell line, which we have 
      previously shown displays a unique calcium influx response, when ER calcium 
      stores are depleted by thapsigargin (TG) treatment. Here, we show that low 
      concentrations of 2-APB failed to induce the rapid augmentation of TG-activated 
      calcium influx previously reported for other cell types. We observed that 
      store-operated calcium (SOC) channels in the A549 cell line exhibited short-term 
      sensitivity to low doses of 2-APB, perhaps reflecting a delayed augmentation of 
      SOC channel activity or the recruitment of 2-APB-insensitive SOC channels. In 
      both intact and permeabilized cells, 2-APB effectively discharged a subset of 
      A549 calcium pools corresponding to the hormone-sensitive intracellular calcium 
      stores. The 2-APB-induced calcium release produced a long-lasting perturbation of 
      the adenosine triphosphate (ATP)-releasable calcium pools, effectively uncoupling 
      ATP-activated calcium release even, when stores are replenished with calcium. In 
      contrast to previous reports, we found that disruption of either the actin or 
      microtubule-based cytoskeleton failed to block the 2-APB-induced effects on 
      calcium signaling in A549 cells. Our study describes novel 
      cytoskeletal-independent effects of 2-APB on Ca2+-signaling pathways, revealing 
      differentially sensitive Ca2+-influx pathways and long-term perturbation of 
      hormone-sensitive Ca2+ stores.
FAU - Padar, Shanthala
AU  - Padar S
AD  - Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and 
      Health Sciences, University of the Pacific, Stockton, CA 95211, USA.
FAU - Bose, Diptiman D
AU  - Bose DD
FAU - Livesey, John C
AU  - Livesey JC
FAU - Thomas, David W
AU  - Thomas DW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Actins)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Boron Compounds)
RN  - 0 (Calcium Channels)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 22144-77-0 (Cytochalasin D)
RN  - 56092-81-0 (Ionomycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - KOO5CM684H (Digitonin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actins/metabolism
MH  - Adenocarcinoma/metabolism/pathology
MH  - Adenosine Triphosphate/metabolism
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Boron Compounds/*pharmacology
MH  - Calcium/*metabolism
MH  - Calcium Channels/*metabolism
MH  - Calcium Signaling/*drug effects
MH  - Cell Line, Tumor
MH  - Cytochalasin D/pharmacology
MH  - Cytoskeleton/*metabolism
MH  - Digitonin/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Green Fluorescent Proteins/metabolism
MH  - Humans
MH  - Indicators and Reagents/pharmacology
MH  - Inositol 1,4,5-Trisphosphate/metabolism
MH  - Ionomycin/metabolism
MH  - Lung Neoplasms/*metabolism/pathology
MH  - Microscopy, Confocal
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Paclitaxel/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Time Factors
EDAT- 2005/03/30 09:00
MHDA- 2005/05/12 09:00
CRDT- 2005/03/30 09:00
PHST- 2004/09/25 00:00 [received]
PHST- 2005/01/24 00:00 [accepted]
PHST- 2005/03/30 09:00 [pubmed]
PHST- 2005/05/12 09:00 [medline]
PHST- 2005/03/30 09:00 [entrez]
AID - S0006-2952(05)00064-X [pii]
AID - 10.1016/j.bcp.2005.01.011 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2005 Apr 15;69(8):1177-86. doi: 10.1016/j.bcp.2005.01.011.