Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heart

• Published in: American journal of physiology. Heart and circulatory physiology 2006-04, Vol.290 (4), p.H1587-H1595
• Main Authors: Olson, Aaron K, Protheroe, Kristin N, Segar, Jeffrey L, Scholz, Thomas D
• Format: Article
• Language: English
• Subjects: Animals; Enzyme Activation; Feedback; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Heart Ventricles - embryology; Heart Ventricles - enzymology; Hemostasis; Hypertrophy, Left Ventricular - embryology; Hypertrophy, Left Ventricular - enzymology; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases - metabolism; Sheep; Tissue Distribution; Ventricular Dysfunction, Left - embryology; Ventricular Dysfunction, Left - enzymology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00984.2005

Department of Pediatrics, Univeristy of Iowa, Iowa City, Iowa Submitted 14 September 2005 ; accepted in final form 10 November 2005 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. hypertrophy; hyperplasia; extracellular signal regulated kinase; c-Jun NH 2 -terminal kinase; p38 Address for reprint requests and other correspondence: T. D. Scholz, Dept. of Pediatrics, Univ. of Iowa, 200 Hawkins Dr., Iowa City, IA 52242 (e-mail: thomas-scholz{at}uiowa.edu )