Estradiol-induced Nongenomic Calcium Signaling Regulates Genotropic Signaling in Macrophages

• Published in: The Journal of biological chemistry Vol. 277; no. 9; pp. 7044 - 7050
• Main Authors: Guo, Zhiyong, Krücken, Jürgen, Benten, W. Peter M., Wunderlich, Frank
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2002; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Calcium - metabolism; Cell Line; Cell Membrane - metabolism; Cell Nucleus - metabolism; Cells, Cultured; Down-Regulation; Endoplasmic Reticulum - metabolism; estradiol; Estradiol - pharmacology; Flow Cytometry; Lipopolysaccharides - metabolism; Macrophages - metabolism; MAP Kinase Signaling System; Mice; Microscopy, Confocal; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; Nitric Oxide - metabolism; p38 Mitogen-Activated Protein Kinases; Promoter Regions, Genetic; Proto-Oncogene Proteins c-fos - metabolism; Receptors, Estrogen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Time Factors; Tissue Distribution; Transfection; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109808200

Estradiol (E2) exerts not only genotropic but also nongenomic actions through nuclear estrogen receptors (ER). Here, we provide a novel paradigm for nongenomic E2 signaling independent of nuclear ER. E2induces a rapid rise in the intracellular free Ca2+concentration ([Ca2+] i) through membrane estrogen receptors in murine RAW 264.7 macrophages. This E2-induced Ca2+ signaling is not prevented by different ER blockers and cannot directly activate stably transfected c-fospromoter or the mitogen-activated protein kinases p38, ERK1/2, and SAPK/JNK, or NO production. However, the E2-induced rise in [Ca2+] 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 E2-changed activation of c-fos promoter can be prevented by an intracellular Ca2+ chelator. Our data indicate that E2-induced nongenomic Ca2+ signaling through membrane ER is able to specifically modulate genotropic signaling pathways with impact on macrophage activation.