Alterations in calcium metabolism in murine macrophages by the benzene metabolite 1,4-benzoquinone.
Exposure of murine peritoneal macrophages to very low concentrations of 1,4-benzoquinone (BQ) induced immediate increases in intracellular Ca2+ concentrations ([Ca2+]i). Increases in [Ca2+]i were induced by concentrations as low as 5 nM and the response was dose dependent and linear up to 1 microM. The sources of Ca2+ were from both internal inositol triphosphate (IP3)-sensitive and -insensitive sites and from the external medium. BQ did not induce IP3 formation and did not affect binding to its receptors. 1, 4-Hydroquinone had no effect on [Ca2+]i. Catechol did elicit some increases in [Ca2+]i, but did so only at much higher concentrations (5 microM). The action of BQ was almost identical to that of the established Ca2+-ATPase inhibitor thapsigargin except that there were some intracellular stores of Ca2+ released by thapsigargin that were not released by BQ. BQ also was mitogenic for macrophages in conjunction with phorbol myristate acetate. These data suggest that BQ raises [Ca2+]i by inhibition of Ca2+-ATPases, is a comitogen, and does so at concentrations that could be achieved in vivo in the general urban population.
Department of Pathology, Duke University Medical Center, Durham, North Carolina, 27710, USA.
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Misra
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Gawdi
J G
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Lewis
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Pizzo
D000818:Animals; D016227:Benzoquinones / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002273:Carcinogens / Q000633:toxicity; D002396:Catechols / Q000633:toxicity; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity; D005978:Glutathione / Q000494:pharmacology; D006873:Hydroquinones / Q000633:toxicity; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000096:biosynthesis*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D019284:Thapsigargin / Q000633:toxicity
D016227:Benzoquinones; D015220:Calcium Channels; D002273:Carcinogens; D002396:Catechols; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009153:Mutagens; D018160:Receptors, Cytoplasmic and Nuclear; D013439:Sulfhydryl Reagents; C004532:quinone; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D005978:Glutathione; C034221:catechol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004229:Dithiothreitol; C031927:hydroquinone