Early impairment of calcium handling and altered expression of junctin
in hearts of mice overexpressing the beta1-adrenergic receptor
S. Engelhardt, P. Boknik, U. Keller, J. Neumann, M. Lohse, and L. Hein. FASEB J, 15 (14):
2718-20(December 2001)Engelhardt, S Boknik, P Keller, U Neumann, J Lohse, M J Hein, L United
States The FASEB journal : official publication of the Federation
of American Societies for Experimental Biology FASEB J. 2001 Dec;15(14):2718-20.
Epub 2001 Oct 15..
Abstract
Chronic stimulation of cardiac beta1-adrenergic receptors contributes
to disease progression and mortality in patients and animal models
of heart failure. To search for the mechanism of adrenergic impairment
of cardiac function in vivo, we studied transgenic mice with cardiac-specific
overexpression of beta1-adrenergic receptors. Transgenic mice with
cardiac overexpression of beta1-adrenergic receptors showed progressive
left ventricular fibrosis starting at 4 months of age. Left ventricular
catheterization revealed a modest enhancement of contractility and
relaxation at 2 months of age, followed by progressive dysfunction
in both parameters and ultimately cardiac failure. When the effects
of endogenous catecholamines were blocked by the b-receptor antagonist
propranolol, maximal rate of contractility (dp/dtmax) and maximal
rate of relaxation (dp/dtmin) were significantly blunted in 2-month-old
beta1-receptor transgenic mice. Isolated cardiomyocytes from these
animals displayed markedly altered calcium transients with significant
prolongation of the intracellular calcium transient compared with
nontransgenic littermates. We determined the expression of sarcoplasmic
reticulum proteins involved in calcium handling by RNase protection
assay and by immunoblotting. Although the expression of calsequestrin,
triadin, and phospholamban was not altered, we observed a progressive
decrease in junctin abundance in beta1-receptor transgenic mice (Pbeta1-adrenergic
receptors.
Engelhardt, S Boknik, P Keller, U Neumann, J Lohse, M J Hein, L United
States The FASEB journal : official publication of the Federation
of American Societies for Experimental Biology FASEB J. 2001 Dec;15(14):2718-20.
Epub 2001 Oct 15.
%0 Journal Article
%1 Engelhardt2001
%A Engelhardt, S.
%A Boknik, P.
%A Keller, U.
%A Neumann, J.
%A Lohse, M. J.
%A Hein, L.
%D 2001
%J FASEB J
%K *Membrane *Mixed ATPases ATPases/genetics/metabolism Animals Blood Blotting, Calcium-Binding Calcium-Transporting Calcium/*metabolism Carrier Contraction/physiology Developmental Expression Factors Function Gene Humans Hypertrophy, Left Messenger/genetics/metabolism Mice Muscle Myocardial Myocardium/cytology/*metabolism Oxygenases Pressure/physiology Proteins Proteins/genetics/metabolism RNA, Regulation Regulation, Reticulum Reticulum/metabolism Sarcoplasmic Time Transgenic Ventricular/genetics/metabolism/physiopathology Western beta-1/*genetics/physiology Receptor Adrenergic
%N 14
%P 2718-20
%T Early impairment of calcium handling and altered expression of junctin
in hearts of mice overexpressing the beta1-adrenergic receptor
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11606476
%V 15
%X Chronic stimulation of cardiac beta1-adrenergic receptors contributes
to disease progression and mortality in patients and animal models
of heart failure. To search for the mechanism of adrenergic impairment
of cardiac function in vivo, we studied transgenic mice with cardiac-specific
overexpression of beta1-adrenergic receptors. Transgenic mice with
cardiac overexpression of beta1-adrenergic receptors showed progressive
left ventricular fibrosis starting at 4 months of age. Left ventricular
catheterization revealed a modest enhancement of contractility and
relaxation at 2 months of age, followed by progressive dysfunction
in both parameters and ultimately cardiac failure. When the effects
of endogenous catecholamines were blocked by the b-receptor antagonist
propranolol, maximal rate of contractility (dp/dtmax) and maximal
rate of relaxation (dp/dtmin) were significantly blunted in 2-month-old
beta1-receptor transgenic mice. Isolated cardiomyocytes from these
animals displayed markedly altered calcium transients with significant
prolongation of the intracellular calcium transient compared with
nontransgenic littermates. We determined the expression of sarcoplasmic
reticulum proteins involved in calcium handling by RNase protection
assay and by immunoblotting. Although the expression of calsequestrin,
triadin, and phospholamban was not altered, we observed a progressive
decrease in junctin abundance in beta1-receptor transgenic mice (Pbeta1-adrenergic
receptors.
@article{Engelhardt2001,
abstract = {Chronic stimulation of cardiac beta1-adrenergic receptors contributes
to disease progression and mortality in patients and animal models
of heart failure. To search for the mechanism of adrenergic impairment
of cardiac function in vivo, we studied transgenic mice with cardiac-specific
overexpression of beta1-adrenergic receptors. Transgenic mice with
cardiac overexpression of beta1-adrenergic receptors showed progressive
left ventricular fibrosis starting at 4 months of age. Left ventricular
catheterization revealed a modest enhancement of contractility and
relaxation at 2 months of age, followed by progressive dysfunction
in both parameters and ultimately cardiac failure. When the effects
of endogenous catecholamines were blocked by the b-receptor antagonist
propranolol, maximal rate of contractility (dp/dtmax) and maximal
rate of relaxation (dp/dtmin) were significantly blunted in 2-month-old
beta1-receptor transgenic mice. Isolated cardiomyocytes from these
animals displayed markedly altered calcium transients with significant
prolongation of the intracellular calcium transient compared with
nontransgenic littermates. We determined the expression of sarcoplasmic
reticulum proteins involved in calcium handling by RNase protection
assay and by immunoblotting. Although the expression of calsequestrin,
triadin, and phospholamban was not altered, we observed a progressive
decrease in junctin abundance in beta1-receptor transgenic mice (Pbeta1-adrenergic
receptors.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Engelhardt, S. and Boknik, P. and Keller, U. and Neumann, J. and Lohse, M. J. and Hein, L.},
biburl = {https://www.bibsonomy.org/bibtex/295db7ee54150991cc6c8d062b81bfee9/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {21cba2dbd74b3141f5b101394ac27ce3},
intrahash = {95db7ee54150991cc6c8d062b81bfee9},
issn = {1530-6860 (Electronic) 1530-6860 (Linking)},
journal = {FASEB J},
keywords = {*Membrane *Mixed ATPases ATPases/genetics/metabolism Animals Blood Blotting, Calcium-Binding Calcium-Transporting Calcium/*metabolism Carrier Contraction/physiology Developmental Expression Factors Function Gene Humans Hypertrophy, Left Messenger/genetics/metabolism Mice Muscle Myocardial Myocardium/cytology/*metabolism Oxygenases Pressure/physiology Proteins Proteins/genetics/metabolism RNA, Regulation Regulation, Reticulum Reticulum/metabolism Sarcoplasmic Time Transgenic Ventricular/genetics/metabolism/physiopathology Western beta-1/*genetics/physiology Receptor Adrenergic},
month = Dec,
note = {Engelhardt, S Boknik, P Keller, U Neumann, J Lohse, M J Hein, L United
States The FASEB journal : official publication of the Federation
of American Societies for Experimental Biology FASEB J. 2001 Dec;15(14):2718-20.
Epub 2001 Oct 15.},
number = 14,
pages = {2718-20},
shorttitle = {Early impairment of calcium handling and altered expression of junctin
in hearts of mice overexpressing the beta1-adrenergic receptor},
timestamp = {2010-12-14T18:22:39.000+0100},
title = {Early impairment of calcium handling and altered expression of junctin
in hearts of mice overexpressing the beta1-adrenergic receptor},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11606476},
volume = 15,
year = 2001
}