Superoxide anion impairs Ca(2+) mobilization in cultured human nasal epithelial cells.
We examined the effects of superoxide anion (O(-2)) on the intracellular Ca(2+) concentration in cultured human nasal epithelial cells. The cells were exposed to O(-2) by pretreatment with xanthine (X) and xanthine oxidase (XO); control cells were treated with X alone. When Ca(2+)-containing Krebs solution was reperfused in the thapsigargin-treated, store-depleted cells, reapplication-induced intracellular Ca(2+) concentration elevation was significantly smaller in X/XO-treated cells than in the control cells, suggesting that O(-2) impairs Ca(2+) release-activated Ca(2+) entry (CRAC). Bath application of ATP induced a steep Ca(2+) transient in both control and X/XO-treated cells. However, the concentration-response curve of the ATP-induced Ca(2+) transient was shifted to a higher concentration in X/XO-treated cells. The impairments of CRAC and ATP-induced Ca(2+) transient induced by X/XO were reversed by superoxide dismutase. Furthermore, all these X/XO-induced effects were also observed in cells pretreated with pyrogallol, also an O(-2) donor. These results indicate that O(-2) impairs at least two mechanisms involved in Ca(2+) mobilization in human nasal epithelial cells, i.e., CRAC and ATP-induced Ca(2+) release.
Koyama
T
T
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Oike
M
M
Komiyama
S
S
Ito
Y
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D009296:Nasal Cavity / Q000166:cytology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013481:Superoxides; D019820:Xanthine; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D000252:Calcium-Transporting ATPases; D002118:Calcium