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The Mitogen-Activated Protein Kinases and Akt Are Developmentally Regulated in the Chronically Anemic Fetal Sheep Heart

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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) infetal sheep (term = 145 days), following which protein levels of total and active Akt, extracellular signal-regulated kinase 1/2 (ERK1 /2), c-fun NH2-terminal kinase (JNK), andp38 were determined in the right and left ventricle (RVand LV). RVprotein-to-DMA 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.

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Authors and Affiliations

  1. Department of Pediatrics, Carver College of Medicine, University of Iowa, 200 Hawkins Dr., Iowa City, IA, 52242, USA

    Aaron K. Olson MD, Kristen N. Protheroe, Thomas D. Scholz MD & Jeffrey L. Segar MD

Authors
  1. Aaron K. Olson MD
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  2. Kristen N. Protheroe
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  3. Thomas D. Scholz MD
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  4. Jeffrey L. Segar MD
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Corresponding author

Correspondence to Jeffrey L. Segar MD.

Additional information

Supported by the following awards from the National Institutes of Health: T32-HL- 07413 (A.K.O.), R01-HL-64770 (J.L.S.), and K02-HL-04495 (T.D.S.).

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Olson, A.K., Protheroe, K.N., Scholz, T.D. et al. The Mitogen-Activated Protein Kinases and Akt Are Developmentally Regulated in the Chronically Anemic Fetal Sheep Heart. Reprod. Sci. 13, 157–165 (2006). https://doi.org/10.1016/j.jsgi.2006.01.004

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  • DOI: https://doi.org/10.1016/j.jsgi.2006.01.004

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