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2018 | 65 | 3 | 409-414
Article title

Sp1 mediates phorbol ester (PMA)-induced expression of membrane-bound guanylyl cyclase GC-A in human monocytic THP-1 cells

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Cyclic guanosine monophosphate (cGMP) is synthesized by two types of enzymes: particulate (membrane-bound) guanylyl cyclases (pGCs) and soluble (cytosolic) guanylyl cyclases (sGCs). sGCs are primarily activated by binding of nitric oxide to their prosthetic heme group while pGCs are activated by binding of peptide ligands to their extracellular domains. One of them, pGC type A (GC-A) is activated by atrial and brain natriuretic peptides (ANP and BNP, respectively). Human monocytes isolated from peripheral blood mononuclear cells have been found to display sGC expression without concomitant expression of GC-A. However, GC-A activity appears in monocytes under certain conditions but a molecular mechanism of GC-A expression is still poorly understood. In this report we show that phorbol ester (PMA) induces transcription of a gene encoding GC-A in human monocytic THP-1 cells. Moreover, we find that PMA-treated THP-1 cells raise cGMP content following treatment with ANP. Studies using pharmacological inhibitors of protein kinases suggest involvement of protein kinase C (PKC), mitogen extracellular kinases (MEK1/2), and extracellular signal-regulated kinases (ERK1/2) in PMA-induced expression of the GC-A encoding gene in THP-1 cells. Finally, we show that PMA stimulates binding of Sp1 transcription factor to GC-rich DNA sequences and mithramycin A (a selective Sp1 inhibitor) inhibits expression of the GC-A mRNA in PMA-treated THP-1 cells. Taken together, our findings suggest that the PMA-stimulated PKC and MEK/ERK signaling pathways induce Sp1-mediated transcription of the GC-A encoding gene in human monocytic THP-1 cells.
Physical description
  • Laboratory of Signal Transduction Molecules, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
  • Department of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland
  • Laboratory of Signal Transduction Molecules, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
  • Laboratory of Signal Transduction Molecules, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
  • Laboratory of Signal Transduction Molecules, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
  • Laboratory of Signal Transduction Molecules, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
  • Nanobioengineering Laboratory, Wrocław Research Centre EIT+, Wrocław, Poland
  • Bender AT, Ostenson CL, Giordano D, Beavo JA (2004) Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression. Cell Signal 16: 365-374.
  • Chu S (2012) Transcriptional regulation by post-transcriptional modification. Role of phosphorylation in Sp1 transcriptional activity. Gene 508: 1-8. doi: 10.1016/j.gene.2012.07.022.
  • Dieter P, Schwende H (2000) Protein kinase C-alpha and -beta play antagonistic roles in the differentiation process of THP-1 cells. Cell Signal 12: 297-302.
  • Dolfini D, Gatta R, Mantovani R (2012) NF-Y and the transcriptional activation of CCAAT promoters. Crit Rev Biochem Mol Biol 47: 29-49 doi: 10.3109/10409238.2011.628970.
  • Garg R, Oliver PM, Maeda N, Pandey KN (2002) Genomic structure, organization, and promoter region analysis of murine guanylyl cyclase/atrial natriuretic peptide receptor-A gene. Gene 291: 123-133.
  • Glezeva N, Collier P, Voon V, Ledwidge M, McDonald K, Watson C, Baugh J (2013) Attenuation of monocyte chemotaxis - a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide. J Cardiovasc Transl Res 6: 545-557. doi: 10.1007/s12265-013-9456-1.
  • Kiemer AK, Hartung T, Vollmar AM (2000) cGMP-mediated inhibition of TNF-α production by the atrial natriuretic peptide in murine macrophages. J Immunol 165: 175-181.
  • Kobiałka M, Witwicka H, Siednienko J, Gorczyca WA (2003) Metabolism of cyclic GMP in peritoneal macrophages of rat and guinea pig. Acta Biochim Pol 50: 837-848.
  • Kumar P, Bolden GR, Pandey KN (2010) Interactive roles of Ets-1, Sp1, and acetylated histones in retinoic acid-dependent activation of guanylyl cyclase/atrial natriuretic peptide receptor-A gene transcription. J Biol Chem 285: 37521-37530. doi: 10.1074/jbc.M110.132795.
  • Kumar P, Tripathi S, Pandey KN (2014) Histone deacetylase inhibitors modulate the transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-a gene: interactive roles of modified histones, histone acetyltransferase, p300, and Sp1. J Biol Chem 289: 6991-7002. doi: 10.1074/jbc.M113.511444.
  • Ladetzki-Baehs K, Keller M, Kiemer AK, Koch E, Zahler S, Wendel A, Vollmar AM (2007) Atrial natriuretic peptide, a regulator of nuclear factor-κB activation in vivo. Endocrinology 148: 332-336.
  • Liang F, Schaufele F, Gardner DG (2001) Functional interaction of NF-Y and Sp1 is required for type a natriuretic peptide receptor gene transcription. J Biol Chem 276: 1516-1522.
  • Liang F, Schaufele F, Gardner DG (1999) Sp1 dependence of natriuretic peptide receptor A gene transcription in rat aortic smooth muscle cells. Endocrinology 140: 1695-1701.
  • Licata A, Corrao S, Petta S, Genco C, Cardillo M, Calvaruso V, Cabibbo G, Massenti F, Cammà C, Licata G, Craxì A (2013) NT pro BNP plasma level and atrial volume are linked to the severity of liver cirrhosis. PLoS One 8: e68364. doi: 10.1371/journal.pone.0068364.
  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
  • Mezzasoma L, Antognelli C, Talesa VN (2016) Atrial natriuretic peptide down-regulates LPS/ATP-mediated IL-1β release by inhibiting NF- kB, NLRP3 inflammasome and caspase-1 activation in THP-1 cells. Immunol Res 64: 303-312. doi: 10.1007/s12026-015-8751-0.
  • Miranda MB, Johnson DE (2002) Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of myeloid cell lines. Leukemia 16: 683-692.
  • Mitkiewicz M, Kuropatwa M, Kurowska E, Gorczyca WA (2011) Different effects of soluble and particulate guanylyl cyclases on expression of inflammatory cytokines in rat peripheral blood mononuclear cells. Immunobiology 216: 423-430. doi: 10.1016/j.imbio.2010.06.006.
  • Morita R, Ukyo N, Furuya M, Uchiyama T, Hori T (2003) Atrial natriuretic peptide polarizes human dendritic cells toward a Th2-promoting phenotype through its receptor guanylyl cyclase-coupled receptor A. J Immunol 170: 5869-5875.
  • Nojiri T, Hosoda H, Tokudome T, Miura K, Ishikane S, Kimura T, Shintani Y, Inoue M, Sawabata N, Miyazato M, Okumura M, Kangawa K (2014) Atrial natriuretic peptide inhibits lipopolysaccharide-induced acute lung injury. Pulm Pharmacol Ther 29: 24-30. doi: 10.1016/j.pupt.2014.01.003.
  • Pandey KN (2011) The functional genomics of guanylyl cyclase/natriuretic peptide receptor-A: perspectives and paradigms. FEBS J 278: 1792-1807. doi: 10.1111/j.1742-4658.2011.08081.x.
  • Pilz RB, Casteel DE (2003) Regulation of gene expression by cyclic GMP. Circ Res 93: 1034-1046.
  • Potter LR, Abbey-Hosch S, Dickey DM (2006) Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev 27: 47-72.
  • Su J, Scholz PM, Weiss HR (2005) Differential effects of cGMP produced by soluble and particulate guanylyl cyclase on mouse ventricular myocytes. Exp Biol Med (Maywood) 230: 242-250.
  • Szabó T, Postrach E, Mähler A, Kung T, Turhan G, von Haehling S, Anker SD, Boschmann M, Doehner W (2013) Increased catabolic activity in adipose tissue of patients with chronic heart failure. Eur J Heart Fail 15: 1131-1137. doi: 10.1093/eurjhf/hft067.
  • Yamaguchi M, Rutledge LJ, Garbers DL (1990) The primary structure of the rat guanylyl cyclase A/atrial natriuretic peptide receptor gene. J Biol Chem 265: 20414-20420.
  • Zolle O, Lawrie AM, Simpson AW (2000) Activation of the particulate and not the soluble guanylate cyclase leads to the inhibition of Ca2+ extrusion through localized elevation of cGMP. J Biol Chem 275: 25892-25899.
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