| Akt and MAPK signaling mediate pregnancy-induced cardiac adaptation. | |
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MedLine Citation:
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PMID: 22345431 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although the signaling pathways underlying exercise-induced cardiac adaptation have been extensively studied, little is known about the molecular mechanisms that result in the response of the heart to pregnancy. The objective of this study was to define the morphological, functional, and gene expression patterns that define the hearts of pregnant mice, and to identify the signaling pathways that mediate this response. Mice were divided into three groups: nonpregnant diestrus control, midpregnancy, and late pregnancy. Both time points of pregnancy were associated with significant cardiac hypertrophy. The prosurvival signaling cascades of Akt and ERK1/2 were activated in the hearts of pregnant mice, while the stress kinase, p38, was decreased. Given the activation of Akt in pregnancy and its known role in cardiac hypertrophy, the hypertrophic response to pregnancy was tested in mice expressing a cardiac-specific activated (myristoylated) form of Akt (myrAkt) or a cardiac-specific constitutively active (antipathologic hypertrophic) form of its downstream target, glycogen synthase kinase 3β (caGSK3β). The pregnancy-induced hypertrophic responses of hearts from these mice were significantly attenuated. Finally, we tested whether pregnancy-associated sex hormones could induce hypertrophy and alter signaling pathways in isolated neonatal rat ventricular myocytes (NRVMs). In fact, progesterone, but not estradiol treatment increased NRVM cell size via phosphorylation of ERK1/2. Inhibition of MEK1 effectively blocked progesterone-induced cellular hypertrophy. Taken together, our study demonstrates that pregnancy-induced cardiac hypertrophy is mediated by activation of Akt and ERK1/2 pathways. |
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Authors:
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Eunhee Chung; Fan Yeung; Leslie A Leinwand |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-02-16 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 112 ISSN: 1522-1601 ISO Abbreviation: J. Appl. Physiol. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-02 Completed Date: 2012-08-27 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 1564-75 Citation Subset: IM |
Affiliation:
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Department of Molecular, Cellular, and Developmental Biology and Biofrontiers Institute, University of Colorado, Boulder, Colorado 80309-0347, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Physiological Animals Cardiomegaly / enzymology*, genetics, pathology, ultrasonography Cells, Cultured Enzyme Activation Estradiol / blood, pharmacology Female Gestational Age Glycogen Synthase Kinase 3 / genetics, metabolism MAP Kinase Signaling System* / drug effects, genetics Mice Mice, Inbred C57BL Mice, Transgenic Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Mitogen-Activated Protein Kinases / genetics, metabolism* Myocytes, Cardiac / drug effects, enzymology*, pathology Phosphorylation Pregnancy Pregnancy Complications, Cardiovascular / enzymology*, genetics, pathology, ultrasonography Progesterone / blood, pharmacology Proto-Oncogene Proteins c-akt / genetics, metabolism* Rats Ribosomal Protein S6 Kinases, 70-kDa / metabolism TOR Serine-Threonine Kinases / metabolism Time Factors p38 Mitogen-Activated Protein Kinases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-50560/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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50-28-2/Estradiol; 57-83-0/Progesterone; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.24/Mapk1 protein, mouse; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
| Comments/Corrections | |
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