Physiol. Genomics Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Physiol. Genomics (August 5, 2003). doi:10.1152/physiolgenomics.00076.2003
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
15/2/142    most recent
00076.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dobson, Jr., J. G
Right arrow Articles by Pratt, R. E
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dobson, Jr., J. G
Right arrow Articles by Pratt, R. E
Submitted on April 30, 2003
Accepted on July 30, 2003

MOLECULAR MECHANISMS OF REDUCED {beta}-ADRENERGIC SIGNALING IN THE AGED HEART AS REVEALED BY GENOMIC PROFILING

James G Dobson, Jr.1*, John Fray2, Jack L Leonard2, and Richard E Pratt3

1 The Genomic Physiology Group, Department of Physiology, University of Massachusetts Medical School, Worcester, MA, USA; Laboratory of Genetic Physiology, Department of Medicine, Brigham and women's Hospital, Boston, MA, USA
2 The Genomic Physiology Group, Department of Physiology, University of Massachusetts Medical School, Worcester, MA, USA
3 Laboratory of Genetic Physiology, Department of Medicine, Brigham and women's Hospital, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: james.dobson{at}umassmed.edu.

Myocardial aging leads to a reduction of {beta}-adrenergic receptor-induced metabolic and contractile responsiveness. We hypothesize that a change in the patterns of gene expression is important in these age-related events. To test this, hearts were harvested from young and aged male rats (3-4 and 20-22 months, respectively). Total mRNA was extracted and prepared for hybridization to Affymetrix U-34A GeneChips. Filtering criteria, involving fold-change and a statistical significance cutoff were employed, yielding 263 probe pairs exhibiting differential signals. Of the 163 annotated genes, at least 56 (34%) were classified as signaling/cell communication. Of these 56, approximately half were directly involved in G protein coupled receptor signaling pathways. We next determined which of these changes might be involved in anti-adrenergic activity and identified 19 potentially important gene products. Importantly, we observed a decrease in {beta}1 adrenergic receptor and adenylyl cyclase mRNAs while the mRNA encoding{beta} arrestin increased. Furthermore, the results demonstrate an increase in mRNAs encoding the adenosine A1 receptor and phospholipase D, which could increase anti-adrenergic effects. Moreover, the mRNAs encoding the muscarinic M3 receptor, nicotinic acetylcholine receptor beta3 and nicotinic acetylcholine receptor related protein were increased as was the mRNA encoding guanylate kinase associated protein. Interestingly, we also observed 8 mRNAs whose abundance changed 3-6 fold with aging that could be considered as being compensatory. While these results do not prove causality, they demonstrate that cardiac aging is associated with changes in the profiles of gene expression and that many of these changes may contribute to reduced adrenergic signaling.




This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
A. Csiszar, M. Wang, E. G. Lakatta, and Z. Ungvari
Inflammation and endothelial dysfunction during aging: role of NF-{kappa}B
J Appl Physiol, October 1, 2008; 105(4): 1333 - 1341.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. S. Fernandez-Twinn, S. Ekizoglou, A. Wayman, C. J. Petry, and S. E. Ozanne
Maternal low-protein diet programs cardiac beta-adrenergic response and signaling in 3-mo-old male offspring
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R429 - R436.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. A. Hacker, S. H. McKiernan, P. S. Douglas, J. Wanagat, and J. M. Aiken
Age-related changes in cardiac structure and function in Fischer 344 x Brown Norway hybrid rats
Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H304 - H311.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
M. Liang and B. Ventura
Physiological genomics in PG and beyond: July to September 2005
Physiol Genomics, October 17, 2005; 23(2): 119 - 124.
[Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S.-K. Park and T. A. Prolla
Gene expression profiling studies of aging in cardiac and skeletal muscles
Cardiovasc Res, May 1, 2005; 66(2): 205 - 212.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
L. Willems, K. J. Ashton, and J. P. Headrick
Adenosine-mediated cardioprotection in the aging myocardium
Cardiovasc Res, May 1, 2005; 66(2): 245 - 255.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
R. J. Sommer, A. J. Hume, J. M. Ciak, J. J. VanNostrand, M. Friggens, and M. K. Walker
Early Developmental 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure Decreases Chick Embryo Heart Chronotropic Response to Isoproterenol but Not to Agents Affecting Signals Downstream of the Beta-Adrenergic Receptor
Toxicol. Sci., February 1, 2005; 83(2): 363 - 371.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.