Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in C6 glioma cells.
The effect of nordihydroguaiaretic acid (NDGA) on Ca(2+) signaling in C6 glioma cells has been investigated. NDGA (5-100 microM) increased [Ca(2+)]i concentration-dependently. The [Ca(2+)]i increase comprised an initial rise and an elevated phase over a time period of 4 min. Removal of extracellular Ca(2+) reduced NDGA-induced [Ca(2+)]i signals by 52+/-2%. After incubation of cells with NDGA in Ca(2+)-free medium for 4 min, addition of 3 mM CaCl2 induced a concentration-dependent increase in [Ca(2+)]i. NDGA (100 microM)-induced [Ca(2+)]i increases in Ca(2+)-containing medium was not changed by pretreatment with 10 microM nifedipine or verapamil. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM) abolished 100 microM NDGA-induced [Ca(2+)]i increases. Inhibition of phospholipase C with 2 microM U73122 had little effect on 100 microM NDGA-induced Ca(2+) release. Several other lipoxygenase inhibitors had no effect on basal [Ca(2+)]i. Collectively, the results suggest that NDGA increased [Ca(2+)]i in glioma cells in a lipoxygenase-independent manner, by releasing Ca(2+) from the endoplasmic reticulum in a manner independent of phospholipase C activity and by causing Ca(2+) influx.
Su
Warren
W
Department of Pediatrics, Pao-Chien General Hospital, Ping Tung, Taiwan.
Tseng
Li-Ling
LL
Lin
Muh-Chiou
MC
Chang
Hsin-Ju
HJ
Lee
Kam-Chung
KC
Chou
Kang-Ju
KJ
Lo
Yuk-Keung
YK
Cheng
Jin-Shiung
JS
Chang
Hong-Tai
HT
Wang
Jue-Long
JL
Liu
Chun-Peng
CP
Chen
Wei-Chung
WC
Jan
Chung-Ren
CR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008084:Lipoxygenase / Q000502:physiology; D009637:Masoprocol / Q000494:pharmacology*; D009994:Osmolar Concentration; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000502:physiology
D009637:Masoprocol; D008084:Lipoxygenase; D010738:Type C Phospholipases; D002118:Calcium