Estradiol-induced nongenomic calcium signaling regulates genotropic signaling in macrophages.
Estradiol (E(2)) exerts not only genotropic but also nongenomic actions through nuclear estrogen receptors (ER). Here, we provide a novel paradigm for nongenomic E(2) signaling independent of nuclear ER. E(2) induces a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) through membrane estrogen receptors in murine RAW 264.7 macrophages. This E(2)-induced Ca(2+) signaling is not prevented by different ER blockers and cannot directly activate stably transfected c-fos promoter or the mitogen-activated protein kinases p38, ERK1/2, and SAPK/JNK, or NO production. However, the E(2)-induced rise in [Ca(2+)](i) specifically down-regulates the serum-stimulated activation of c-fos promoter and ERK1/2, and conversely, it specifically up-regulates lipopolysaccharide-stimulated activation of c-fos promoter, p38, and NO production. The E(2)-changed activation of c-fos promoter can be prevented by an intracellular Ca(2+) chelator. Our data indicate that E(2)-induced nongenomic Ca(2+) signaling through membrane ER is able to specifically modulate genotropic signaling pathways with impact on macrophage activation.
Guo
Zhiyong
Z
Division of Molecular Parasitology, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Düsseldorf, Germany.
Krucken
Jurgen
J
Benten
W Peter M
WP
Wunderlich
Frank
F
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D009569:Nitric Oxide; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium