OBJECTIVE: Heart failure is associated with alterations in contractile
parameters and accompanied by abnormalities in intracellular calcium
homeostasis. Sarcoplasmic reticulum Ca$^2+$ ATPase (SERCA2) and
phospholamban (PLB) are important in intracellular calcium cycling.
The aim of the present study was to examine mechanisms causing reductions
in SERCA2 activity in the failing heart. METHODS: Myocardial infarction
(MI) was induced in male Wistar rats, and animals with congestive
heart failure were examined 6 weeks after the primary operation.
RESULTS: Serine(16) monomeric and pentameric phosphorylated PLB were
significantly downregulated (50 and 55\%, respectively), whereas
threonine(17) phosphorylated PLB was unchanged in failing compared
to sham hearts. Protein phosphatases 1 and 2A were significantly
upregulated (26 and 42\%, respectively) and phosphatase 2C significantly
downregulated (29\%), whereas the level of protein kinase A regulatory
subunit II remained unchanged during heart failure. Increasing PLB
phosphorylation by forskolin in isolated cardiomyocytes after inhibition
of the Na$^+$-Ca$^2+$ exchanger activity had significantly
greater effect on SERCA2 activity in failing than in sham cells (49
and 20\% faster transient decline, respectively). Decreasing PLB
phosphorylation by the protein kinase A inhibitor H89 had significantly
less effect on SERCA2 activity in failing compared to sham cardiomyocytes
(20 and 75\% slower transient decline, respectively). CONCLUSION:
The observed changes in SERCA2 activity after increasing and decreasing
serine(16) PLB phosphorylation in cardiomyocytes from sham and failing
hearts, suggest that the observed reduction in serine(16) PLB phosphorylation
is one major factor determining the reduced SERCA2 activity in heart
failure after MI.
%0 Journal Article
%1 Sand_2002_382
%A Sande, J�rn B
%A Sjaastad, Ivar
%A Hoen, Ingvild B
%A B�kenes, Janny
%A T�nnessen, Theis
%A Holt, Even
%A Lunde, Per K
%A Christensen, Geir
%D 2002
%J Cardiovasc. Res.
%K 11827689 AMP-Dependent ATPase, Adrenergic Animals, Calcium, Calcium-Binding Congestive, Cyclic Enzyme Failure, Fluid, Forskolin, Gov't, Heart Homeostasis, Immunoblotting, Infarction, Inhibitors, Intracellular Isoproterenol, Isoquinolines, Kinases, Male, Myocardial Myocardium, Non-U.S. Phosphorylation, Protein Proteins, Rats, Research Reticulum, Sarcoplasmic Sulfonamides, Support, Wistar, beta-Agonists, {C}a$^{2+}$-Transporting
%N 2
%P 382-91
%T Reduced level of serine(16) phosphorylated phospholamban in the failing
rat myocardium: a major contributor to reduced SERCA2 activity.
%U http://dx.doi.org/10.1016/S0008-6363(01)00489-8
%V 53
%X OBJECTIVE: Heart failure is associated with alterations in contractile
parameters and accompanied by abnormalities in intracellular calcium
homeostasis. Sarcoplasmic reticulum Ca$^2+$ ATPase (SERCA2) and
phospholamban (PLB) are important in intracellular calcium cycling.
The aim of the present study was to examine mechanisms causing reductions
in SERCA2 activity in the failing heart. METHODS: Myocardial infarction
(MI) was induced in male Wistar rats, and animals with congestive
heart failure were examined 6 weeks after the primary operation.
RESULTS: Serine(16) monomeric and pentameric phosphorylated PLB were
significantly downregulated (50 and 55\%, respectively), whereas
threonine(17) phosphorylated PLB was unchanged in failing compared
to sham hearts. Protein phosphatases 1 and 2A were significantly
upregulated (26 and 42\%, respectively) and phosphatase 2C significantly
downregulated (29\%), whereas the level of protein kinase A regulatory
subunit II remained unchanged during heart failure. Increasing PLB
phosphorylation by forskolin in isolated cardiomyocytes after inhibition
of the Na$^+$-Ca$^2+$ exchanger activity had significantly
greater effect on SERCA2 activity in failing than in sham cells (49
and 20\% faster transient decline, respectively). Decreasing PLB
phosphorylation by the protein kinase A inhibitor H89 had significantly
less effect on SERCA2 activity in failing compared to sham cardiomyocytes
(20 and 75\% slower transient decline, respectively). CONCLUSION:
The observed changes in SERCA2 activity after increasing and decreasing
serine(16) PLB phosphorylation in cardiomyocytes from sham and failing
hearts, suggest that the observed reduction in serine(16) PLB phosphorylation
is one major factor determining the reduced SERCA2 activity in heart
failure after MI.
@article{Sand_2002_382,
abstract = {O{BJECTIVE}: Heart failure is associated with alterations in contractile
parameters and accompanied by abnormalities in intracellular calcium
homeostasis. Sarcoplasmic reticulum {C}a$^{2+}$ ATPase (SERCA2) and
phospholamban (PLB) are important in intracellular calcium cycling.
The aim of the present study was to examine mechanisms causing reductions
in SERCA2 activity in the failing heart. METHODS: Myocardial infarction
({MI}) was induced in male Wistar rats, and animals with congestive
heart failure were examined 6 weeks after the primary operation.
RESULTS: Serine(16) monomeric and pentameric phosphorylated PLB were
significantly downregulated (50 and 55\%, respectively), whereas
threonine(17) phosphorylated PLB was unchanged in failing compared
to sham hearts. Protein phosphatases 1 and 2A were significantly
upregulated (26 and 42\%, respectively) and phosphatase 2C significantly
downregulated (29\%), whereas the level of protein kinase A regulatory
subunit II remained unchanged during heart failure. Increasing PLB
phosphorylation by forskolin in isolated cardiomyocytes after inhibition
of the {N}a$^{+}$-{C}a$^{2+}$ exchanger activity had significantly
greater effect on SERCA2 activity in failing than in sham cells (49
and 20\% faster transient decline, respectively). Decreasing PLB
phosphorylation by the protein kinase A inhibitor H89 had significantly
less effect on SERCA2 activity in failing compared to sham cardiomyocytes
(20 and 75\% slower transient decline, respectively). CONCLUSION:
The observed changes in SERCA2 activity after increasing and decreasing
serine(16) PLB phosphorylation in cardiomyocytes from sham and failing
hearts, suggest that the observed reduction in serine(16) PLB phosphorylation
is one major factor determining the reduced SERCA2 activity in heart
failure after {MI}.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Sande, J�rn B and Sjaastad, Ivar and Hoen, Ingvild B and B�kenes, Janny and T�nnessen, Theis and Holt, Even and Lunde, Per K and Christensen, Geir},
biburl = {https://www.bibsonomy.org/bibtex/291ad57e23ffa859fe1b153af6f03b958/hake},
description = {The whole bibliography file I use.},
file = {Sand_2002_382.pdf:Sand_2002_382.pdf:PDF},
interhash = {669778f736fb2843dcacc5ad9fd7e54a},
intrahash = {91ad57e23ffa859fe1b153af6f03b958},
journal = {Cardiovasc. Res.},
key = 31,
keywords = {11827689 AMP-Dependent ATPase, Adrenergic Animals, Calcium, Calcium-Binding Congestive, Cyclic Enzyme Failure, Fluid, Forskolin, Gov't, Heart Homeostasis, Immunoblotting, Infarction, Inhibitors, Intracellular Isoproterenol, Isoquinolines, Kinases, Male, Myocardial Myocardium, Non-U.S. Phosphorylation, Protein Proteins, Rats, Research Reticulum, Sarcoplasmic Sulfonamides, Support, Wistar, beta-Agonists, {C}a$^{2+}$-Transporting},
month = Feb,
number = 2,
pages = {382-91},
pii = {S0008636301004898},
timestamp = {2009-06-03T11:21:28.000+0200},
title = {Reduced level of serine(16) phosphorylated phospholamban in the failing
rat myocardium: a major contributor to reduced SERCA2 activity.},
url = {http://dx.doi.org/10.1016/S0008-6363(01)00489-8},
volume = 53,
year = 2002
}