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The mitogen-activated protein kinases and Akt are developmentally regulated in the chronically anemic fetal sheep heart. J Soc Gynecol Investig 2006 Apr;13(3):157-65

Date

04/28/2006

Pubmed ID

16638585

DOI

10.1016/j.jsgi.2006.01.004

Scopus ID

2-s2.0-33646109563   11 Citations

Abstract

OBJECTIVE: Protein kinase B (Akt) and the mitogen-activated protein kinases (MAPKs) mediate hypertrophy in the adult heart, although their importance in the developing heart is poorly understood. The goal of the current study was to determine if volume loading the fetal heart resulting from chronic anemia affects regulation of Akt and the MAPKs and if this response is developmentally regulated.

METHODS: Anemia was created by 7 days of isovolumic hemorrhage beginning at 101 days (early GA) or 129 days (late GA) gestational age (GA) in fetal sheep (term = 145 days), following which protein levels of total and active Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and p38 were determined in the right and left ventricle (RV and LV). RV protein-to-DNA ratios were also assessed.

RESULTS: At both GAs, ventricular (RV + LV + septum) weight normalized to body weight was significantly increased in anemic fetuses. Anemia had no effect on expression of myocardial total or active Akt, JNK, or p38 at either GA. Levels of total ERK1/2 were also unchanged, although active ERK1/2 was significantly decreased in the late but not early GA anemic fetuses. Total JNK and total and active ERK1/2 and Akt were significantly greater in early versus late GA anemic fetuses. Protein-to-DNA ratios were unchanged in response to anemia at both GAs, but were greater in late GA compared to early GA anemic fetuses.

CONCLUSION: These results identify important developmental differences in the response of the MAPKs and Akt in the stressed fetal heart. Differences in protein-to-DNA ratios likely reflect the different populations of cardiomyocytes composing the fetal heart at these two GAs and their cell-dependent response to a hemodynamic load.

Author List

Olson AK, Protheroe KN, Scholz TD, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anemia
Animals
DNA
Disease Models, Animal
Fetus
Gene Expression Profiling
Gene Expression Regulation, Developmental
Heart
Heart Ventricles
Hemodynamics
Hypertrophy
Immunoblotting
Mitogen-Activated Protein Kinases
Myocardium
Myocytes, Cardiac
Proto-Oncogene Proteins c-akt
Sheep
Signal Transduction
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0