Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/370
Title: Regulation of Placental Leptin Expression by Cyclic Adenosine 5 '-Monophosphate Involves Cross Talk between Protein Kinase A and Mitogen-Activated Protein Kinase Signaling Pathways
Authors: Maymó, Julieta L.
Pérez Pérez, Antonio
Dueñas, José L.
Calvo, Juan Carlos
Sánchez-Margalet, Víctor
Varone, Cecilia L.
metadata.dc.contributor.authoraffiliation: [Maymó,JL;Calvo,JC;Varone,CL] Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales,Universidad de Buenos Aires, Buenos Aires, Argentina [Pérez Pérez,A;Sánchez-Margalet,V] Departamento de Bioquímica Médica y Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina,Universidad de Sevilla, Sevilla, Spain. [Dueñas,JL] Servicio de Ginecología y Obstetricia, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Calvo,JC] Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina
Keywords: Leptin;Adipose tissue;Placenta;Trophoblastic cells;Protein kinase;Female
metadata.dc.subject.mesh: Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotides::Nucleotides, Cyclic::Cyclic AMP
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Cell Cycle Proteins::Cyclin-Dependent Kinases
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzopyrans::Chromones::Flavonoids
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Adipokines::Leptin
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction::MAP Kinase Signaling System
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Organic Chemistry Processes::Phosphorylation
Medical Subject Headings::Anatomy::Embryonic Structures::Placenta
Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Regulatory Sequences, Nucleic Acid::Promoter Regions, Genetic
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Receptor Cross-Talk
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Recombination, Genetic::Transfection
Issue Date: Aug-2010
Publisher: The Endocrine Society
Citation: Maymó JL, Pérez Pérez A, Dueñas A, Calvo JC, Sánchez-Margalet V, Varone CL. Regulation of Placental Leptin Expression by Cyclic Adenosine 5 '-Monophosphate Involves Cross Talk between Protein Kinase A and Mitogen-Activated Protein Kinase Signaling Pathways. Endocrinology. 2010 August; 151(8):3738-5
Abstract: Leptin, a 16-kDa protein mainly produced by adipose tissue, has been involved in the control of energy balance through its hypothalamic receptor. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it was found to be expressed. In the current study, we examined the effect of cAMP in the regulation of leptin expression in trophoblastic cells. We found that dibutyryl cAMP [(Bu)(2)cAMP], a cAMP analog, showed an inducing effect on endogenous leptin expression in BeWo and JEG-3 cell lines when analyzed by Western blot analysis and quantitative RT-PCR. Maximal effect was achieved at 100 microM. Leptin promoter activity was also stimulated, evaluated by transient transfection with a reporter plasmid construction. Similar results were obtained with human term placental explants, thus indicating physiological relevance. Because cAMP usually exerts its actions through activation of protein kinase A (PKA) signaling, this pathway was analyzed. We found that cAMP response element-binding protein (CREB) phosphorylation was significantly increased with (Bu)(2)cAMP treatment. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor CREB caused a significant stimulation on leptin promoter activity. On the other hand, the cotransfection with a dominant negative mutant of the regulatory subunit of PKA inhibited leptin promoter activity. We determined that cAMP effect could be blocked by pharmacologic inhibition of PKA or adenylyl ciclase in BeWo cells and in human placental explants. Thereafter, we decided to investigate the involvement of the MAPK/ERK signaling pathway in the cAMP effect on leptin induction. We found that 50 microm PD98059, a MAPK kinase inhibitor, partially blocked leptin induction by cAMP, measured both by Western blot analysis and reporter transient transfection assay. Moreover, ERK 1/2 phosphorylation was significantly increased with (Bu)(2)cAMP treatment, and this effect was dose dependent. Finally, we observed that 50 microm PD98059 inhibited cAMP-dependent phosphorylation of CREB in placental explants. In summary, we provide some evidence suggesting that cAMP induces leptin expression in placental cells and that this effect seems to be mediated by a cross talk between PKA and MAPK signaling pathways.
URI: http://hdl.handle.net/10668/370
metadata.dc.relation.publisherversion: http://endo.endojournals.org/content/151/8/3738
metadata.dc.identifier.doi: 10.1210/en.2010-0064
ISSN: 1945-7170 (Online)
0013-7227 (Print)
Appears in Collections:01- Artículos - Hospital Virgen Macarena

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