TY - JOUR
T1 - Multiple effects of econazole on calcium signaling
T2 - Depletion of thapsigargin-sensitive calcium store, activation of extracellular calcium influx, and inhibition of capacitative calcium entry
AU - Jan, Chung Ren
AU - Ho, Chin Man
AU - Wu, Sheng Nan
AU - Tseng, Ching Jiunn
PY - 1999/1/11
Y1 - 1999/1/11
N2 - The effect of econazole on intracellular calcium levels ([Ca2+](i)) in Madin Darby canine kidney cells was investigated using fura-2 fluorimetry. Econazole increased [Ca2+](i) dose-dependently at 5-50 μM. The Ca2+ signal consisted of an initial rise, a gradual decay and a sustained plateau. Extracellular Ca2+ removal partially reduced the econazole response. Mn2+ quench of fura-2 fluorescence confirmed econazole-induced Ca2+ influx. The econazole-sensitive intracellular Ca2+ store overlaps with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 25 μM econazole depleted the thapsigargin-sensitive store, and conversely, thapsigargin abolished the econazole response. Econazole (25-50 μM) partially inhibited capacitative Ca2+ entry induced by cyclopiazonic acid, another endoplasmic reticulum Ca2+ pump inhibitor, measured by depleting internal Ca2+ store in Ca2+-free medium followed by adding 10 mM CaCl2. Econazole induced capacitative Ca2+ entry itself. Pretreatment with La3+ (100 μM) partially inhibited 25 μM econazole-induced Mn2+ quench of fura-2 fluorescence, and La3+ immediately reduced 20 μM econazole-induced Ca2+ signal when added at the peak of the signal, suggesting that econazole induced Ca2+ influx via two separate pathways: one is sensitive to La3+, the other is not. La3+ enlarged 25 μM econazole-induced [Ca2+](i) transient during the decay phase. The econazole response was not altered when the cytosolic level of inositol 1,4,5-trisphosphate was inhibited by the phospholipase C inhibitor U73122. Copyright (C) 1999 Elsevier Science B.V.
AB - The effect of econazole on intracellular calcium levels ([Ca2+](i)) in Madin Darby canine kidney cells was investigated using fura-2 fluorimetry. Econazole increased [Ca2+](i) dose-dependently at 5-50 μM. The Ca2+ signal consisted of an initial rise, a gradual decay and a sustained plateau. Extracellular Ca2+ removal partially reduced the econazole response. Mn2+ quench of fura-2 fluorescence confirmed econazole-induced Ca2+ influx. The econazole-sensitive intracellular Ca2+ store overlaps with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 25 μM econazole depleted the thapsigargin-sensitive store, and conversely, thapsigargin abolished the econazole response. Econazole (25-50 μM) partially inhibited capacitative Ca2+ entry induced by cyclopiazonic acid, another endoplasmic reticulum Ca2+ pump inhibitor, measured by depleting internal Ca2+ store in Ca2+-free medium followed by adding 10 mM CaCl2. Econazole induced capacitative Ca2+ entry itself. Pretreatment with La3+ (100 μM) partially inhibited 25 μM econazole-induced Mn2+ quench of fura-2 fluorescence, and La3+ immediately reduced 20 μM econazole-induced Ca2+ signal when added at the peak of the signal, suggesting that econazole induced Ca2+ influx via two separate pathways: one is sensitive to La3+, the other is not. La3+ enlarged 25 μM econazole-induced [Ca2+](i) transient during the decay phase. The econazole response was not altered when the cytosolic level of inositol 1,4,5-trisphosphate was inhibited by the phospholipase C inhibitor U73122. Copyright (C) 1999 Elsevier Science B.V.
KW - Ca signaling
KW - Capacitative Ca entry
KW - Econazole
KW - Fura-2
KW - Madin Darby canine kidney cell
UR - http://www.scopus.com/inward/record.url?scp=0032933437&partnerID=8YFLogxK
U2 - 10.1016/S0167-4889(98)00159-1
DO - 10.1016/S0167-4889(98)00159-1
M3 - 文章
C2 - 9990306
AN - SCOPUS:0032933437
SN - 0167-4889
VL - 1448
SP - 533
EP - 542
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 3
ER -