|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 25, 22892-22900, June 22, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Pediatrics, § Molecular Genetics
and Biochemistry, and ¶ Cardiology, University of Pittsburgh
School of Medicine, Pittsburgh, Pennsylvania 15213, the
The cellular and molecular basis of growth
hormone (GH) actions on the heart remain poorly defined, and it is
unclear whether GH effects on the myocardium are direct or mediated at
least in part via insulin-like growth factor (IGF-1). Here, we
demonstrate that the cultured neonatal cardiomyocyte is not an
appropriate model to study the effects of GH because of artifactual
loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR. Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt
intracellular pathways in the cells expressing GHR. Although exposure
to GH resulted in a significant increase in the size of the
cardiomyocyte and increased expression of c-fos,
myosin light chain 2, and skeletal
Demonstration of Direct Effects of Growth Hormone on Neonatal
Cardiomyocytes*
,,
,
Department of Pediatrics, UCLA School of Medicine,
Los Angeles, California 90095, the ** Department of Medicine,
University of Alabama at Birmingham and Birmingham Veterans Affairs
Medical Center, Birmingham, Alabama 35294, and the
Department of Medicine, McGill University,
Montreal, Quebec, H3A-1A1, Canada
-actin mRNAs, there were no
significant changes in IGF-1 or atrial natriuretic factor
mRNA levels in response to GH stimulation. In this model, GH
increased incorporation of leucine, uptake of palmitic acid, and
abundance of fatty acid transport protein mRNA. In contrast, GH
decreased uptake of 2-deoxy-D-glucose and levels of Glut1
protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in
cellular metabolic profile in the absence of demonstrable changes in
IGF-1 mRNA, suggesting that these effects may be independent of
IGF-1.
*
This work was supported by National Institutes of Health
Grants DK49845 (to R. K. M.), HD25024 and 33997 (to S. U. D.),
DK46395 (to S. J. F.), and T32DK07729, the Children's Hospital of
Pittsburgh, the Vira I. Heinz Foundation, and American Heart
Association Grant 9951280U (to R. K. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Division of
Endocrinology, Department of Pediatrics, Children's Hospital of
Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213. Tel.: 412-692-5806;
Fax: 412-692-6449; E-mail: menonr@chplink.chp.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. R. Reddy, M. J. Pushpanathan, R. F. Ransom, L. B. Holzman, F. C. Brosius III, M. Diakonova, P. Mathieson, M. A. Saleem, E. O. List, J. J. Kopchick, et al. Identification of the Glomerular Podocyte as a Target for Growth Hormone Action Endocrinology, May 1, 2007; 148(5): 2045 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pivonello, M. Galderisi, R. S. Auriemma, M. C. De Martino, M. Galdiero, A. Ciccarelli, A. D'Errico, I. Kourides, P. Burman, G. Lombardi, et al. Treatment with Growth Hormone Receptor Antagonist in Acromegaly: Effect on Cardiac Structure and Performance J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 476 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sotiropoulos, M. Ohanna, C. Kedzia, R. K. Menon, J. J. Kopchick, P. A. Kelly, and M. Pende Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation PNAS, May 9, 2006; 103(19): 7315 - 7320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Cowan, X. Wang, R. Guan, K. He, J. Jiang, G. Baumann, R. A. Black, M. S. Wolfe, and S. J. Frank Growth Hormone Receptor Is a Target for Presenilin-dependent {gamma}-Secretase Cleavage J. Biol. Chem., May 13, 2005; 280(19): 19331 - 19342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jiang, X. Wang, K. He, X. Li, C. Chen, P. P. Sayeski, M. J. Waters, and S. J. Frank A Conformationally Sensitive GHR [Growth Hormone (GH) Receptor] Antibody: Impact on GH Signaling and GHR Proteolysis Mol. Endocrinol., December 1, 2004; 18(12): 2981 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Liebner, A. Cattelino, R. Gallini, N. Rudini, M. Iurlaro, S. Piccolo, and E. Dejana {beta}-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse J. Cell Biol., August 2, 2004; 166(3): 359 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhong, Q. Zhou, D. M. Toivola, G.-Z. Tao, E. Z. Resurreccion, and M. B. Omary Organ-specific stress induces mouse pancreatic keratin overexpression in association with NF-{kappa}B activation J. Cell Sci., May 1, 2004; 117(9): 1709 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Spagnuolo, M. Corada, F. Orsenigo, L. Zanetta, U. Deuschle, P. Sandy, C. Schneider, C. J. Drake, F. Breviario, and E. Dejana Gas1 is induced by VE-cadherin and vascular endothelial growth factor and inhibits endothelial cell apoptosis Blood, April 15, 2004; 103(8): 3005 - 3012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Colao, D. Ferone, P. Marzullo, and G. Lombardi Systemic Complications of Acromegaly: Epidemiology, Pathogenesis, and Management Endocr. Rev., February 1, 2004; 25(1): 102 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iwase, H. Kanazawa, Y. Kato, T. Nishizawa, F. Somura, R. Ishiki, K. Nagata, K. Hashimoto, K. Takagi, H. Izawa, et al. Growth hormone-releasing peptide can improve left ventricular dysfunction and attenuate dilation in dilated cardiomyopathic hamsters Cardiovasc Res, January 1, 2004; 61(1): 30 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Z. Tao, D. M. Toivola, B. Zhong, S. A. Michie, E. Z. Resurreccion, Y. Tamai, M. M. Taketo, and M. B. Omary Keratin-8 null mice have different gallbladder and liver susceptibility to lithogenic diet-induced injury J. Cell Sci., November 15, 2003; 116(22): 4629 - 4638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, K. He, M. Gerhart, J. Jiang, R. J. Paxton, R. K. Menon, R. A. Black, G. Baumann, and S. J. Frank Reduced Proteolysis of Rabbit Growth Hormone (GH) Receptor Substituted with Mouse GH Receptor Cleavage Site Mol. Endocrinol., October 1, 2003; 17(10): 1931 - 1943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rajapurohitam, X. T. Gan, L. A. Kirshenbaum, and M. Karmazyn The Obesity-Associated Peptide Leptin Induces Hypertrophy in Neonatal Rat Ventricular Myocytes Circ. Res., August 22, 2003; 93(4): 277 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Clayton Cardiovascular Function in Acromegaly Endocr. Rev., June 1, 2003; 24(3): 272 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, K. He, M. Gerhart, Y. Huang, J. Jiang, R. J. Paxton, S. Yang, C. Lu, R. K. Menon, R. A. Black, et al. Metalloprotease-mediated GH Receptor Proteolysis and GHBP Shedding. DETERMINATION OF EXTRACELLULAR DOMAIN STEM REGION CLEAVAGE SITE J. Biol. Chem., December 20, 2002; 277(52): 50510 - 50519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cittadini, A. Berggren, S. Longobardi, C. Ehrnborg, R. Napoli, T. Rosen, S. Fazio, K. Caidahl, B.-A. Bengtsson, and L. Sacca Supraphysiological Doses of GH Induce Rapid Changes in Cardiac Morphology and Function J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1654 - 1659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Laufs, H. Kilter, C. Konkol, S. Wassmann, M. Bohm, and G. Nickenig Impact of HMG CoA reductase inhibition on small GTPases in the heart Cardiovasc Res, March 1, 2002; 53(4): 911 - 920. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |