Intracellular Ca2+ pool depletion is linked to the induction of nitric oxide synthesis in murine peritoneal macrophages.
The ability of putative Ca(2+)-ATPase inhibitor of endoplasmic reticulum (ER), thapsigargin (TG), to induce nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. TG alone had small effect on NO synthesis, whereas TG in combination with LPS markedly increased NO synthesis in a dose dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA by Northern blotting. In addition, the ability of TG on NO synthesis could be mimicked by another chemically unrelated inhibitor of Ca(2+)-ATPase, 2,5-DI-(t-butyl)-1, 4-benzohydroquinone (tBuBHQ). Adding EGTA, a calcium chelator, to the incubation medium significantly reduced the ability of macrophages to induce NO synthesis in response to the optimal stimulation of TG or TG plus LPS. These results therefore demonstrate that intracellular Ca2+ pool depletion is linked to the induction of NO synthesis in murine peritoneal macrophages and further suggest that it is also related with interferon-gamma (IFN-gamma)-induced signaling.
Park
Y C
YC
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Korea.
Jun
C D
CD
Kang
H S
HS
Kim
H D
HD
Kim
H M
HM
Chung
H T
HT
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006873:Hydroquinones / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013729:Terpenes; C019359:2,5-di-tert-butylhydroquinone; D009569:Nitric Oxide; D004533:Egtazic Acid; D019284:Thapsigargin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000252:Calcium-Transporting ATPases; D002118:Calcium