Document Detail


Akt and MAPK signaling mediate pregnancy-induced cardiac adaptation.
MedLine Citation:
PMID:  22345431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Eunhee Chung; Fan Yeung; Leslie A Leinwand
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-16
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  112     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-02     Completed Date:  2012-08-27     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1564-75     Citation Subset:  IM    
Affiliation:
Department of Molecular, Cellular, and Developmental Biology and Biofrontiers Institute, University of Colorado, Boulder, Colorado 80309-0347, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
HL-50560/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effects of leptin and obesity on the upper airway function.
Next Document:  Effects of lactate on the voltage-gated sodium channels of rat skeletal muscle: modulating current o...