title: The mitogen-activated protein kinases and Akt are developmentally regulated in the chronically anemic fetal sheep heart.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Olson
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Protheroe
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Scholz
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Segar
mesh_terms: D000740:Anemia / Q000150:complications*; D000818:Animals; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005333:Fetus / Q000201:enzymology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006352:Heart Ventricles / Q000737:chemistry; D006439:Hemodynamics; D006984:Hypertrophy; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000201:enzymology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction
chemical_list: D004247:DNA; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases