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Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heart. Am J Physiol Heart Circ Physiol 2006 Apr;290(4):H1587-95

Date

11/22/2005

Pubmed ID

16299265

DOI

10.1152/ajpheart.00984.2005

Scopus ID

2-s2.0-33646075734   15 Citations

Abstract

The mitogen-activated protein (MAP) kinase signaling pathways help to mediate the hypertrophic response of the pressure-loaded adult heart, although their importance in fetal myocardium is less known. The goal of this study was to determine the role the MAP kinase signaling pathways play in regulating the response of the fetal heart to a pressure load. Aortic (Ao) and pulmonary artery (PA) bands were placed in 132-day fetal sheep for 7 days. Protein levels of the total and active (phosphorylated) terminal MAP kinases extracellular signal-regulated kinase (ERK/P-ERK), c-Jun NH(2)-terminal kinase (JNK/P-JNK), and p38/P-p38 and the MAP kinase phosphatases MKP-1, MKP-2, and MKP-3 were made in the right and left ventricular (RV and LV) free walls. In both Ao- and PA-banded animals, total heart weight normalized to body weight was significantly increased, largely due to an increase in RV free wall mass in the Ao-banded animals and an increase in septal mass in the PA-banded fetuses. Total protein levels of the three terminal kinases and of P-ERK and P-JNK remained stable in both groups of banded animals. However, P-p38 was significantly increased in RV and LV of Ao- and PA-banded fetuses. Whereas MKP-1 and MKP-2 protein levels were unchanged following Ao- and PA-banding, MKP-3 protein levels were significantly increased in the RV of the PA-banded animals. These findings indicate that the MAP kinase signaling pathways are active in the fetal heart and help to modulate the response of prenatal myocardium to a pressure load.

Author List

Olson AK, Protheroe KN, Segar JL, Scholz TD

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

Animals
Enzyme Activation
Feedback
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Heart Ventricles
Hemostasis
Hypertrophy, Left Ventricular
MAP Kinase Signaling System
Mitogen-Activated Protein Kinases
Sheep
Tissue Distribution
Ventricular Dysfunction, Left
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0