Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation
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Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation. / Shanmugam, Mayilvahanan; Molina, Cristina E; Gao, Shumin; Severac-Bastide, Renaud; Fischmeister, Rodolphe; Babu, Gopal J.
In: BIOCHEM BIOPH RES CO, Vol. 410, No. 1, 24.06.2011, p. 97-101.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation
AU - Shanmugam, Mayilvahanan
AU - Molina, Cristina E
AU - Gao, Shumin
AU - Severac-Bastide, Renaud
AU - Fischmeister, Rodolphe
AU - Babu, Gopal J
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/6/24
Y1 - 2011/6/24
N2 - Sarcolipin (SLN), a key regulator of cardiac sarco(endo)plasmic reticulum (SR) Ca(2+) ATPase, is predominantly expressed in atria and mediates β-adrenergic responses. Studies have shown that SLN mRNA expression is decreased in human chronic atrial fibrillation (AF) and in aortic banded mouse atria; however, SLN protein expression in human atrial pathology and its role in atrial SR Ca(2+) uptake are not yet elucidated. In the present study, we determined the expression of major SR Ca(2+) handling proteins in atria of human AF patients and in human and in a mouse model of heart failure (HF). We found that the expression of SR Ca(2+) uptake and Ca(2+) release channel proteins are significantly decreased in atria but not in the ventricles of pressure-overload induced HF in mice. In human AF and HF, the expression of SLN protein was significantly decreased; whereas the expressions of other major SR Ca(2+) handling proteins were not altered. Further, we found that the SR Ca(2+) uptake was significantly increased in human AF. The selective downregulation of SLN and enhanced SR Ca(2+) uptake in human AF suggest that SLN downregulation could play an important role in abnormal intracellular Ca(2+) cycling in atrial pathology.
AB - Sarcolipin (SLN), a key regulator of cardiac sarco(endo)plasmic reticulum (SR) Ca(2+) ATPase, is predominantly expressed in atria and mediates β-adrenergic responses. Studies have shown that SLN mRNA expression is decreased in human chronic atrial fibrillation (AF) and in aortic banded mouse atria; however, SLN protein expression in human atrial pathology and its role in atrial SR Ca(2+) uptake are not yet elucidated. In the present study, we determined the expression of major SR Ca(2+) handling proteins in atria of human AF patients and in human and in a mouse model of heart failure (HF). We found that the expression of SR Ca(2+) uptake and Ca(2+) release channel proteins are significantly decreased in atria but not in the ventricles of pressure-overload induced HF in mice. In human AF and HF, the expression of SLN protein was significantly decreased; whereas the expressions of other major SR Ca(2+) handling proteins were not altered. Further, we found that the SR Ca(2+) uptake was significantly increased in human AF. The selective downregulation of SLN and enhanced SR Ca(2+) uptake in human AF suggest that SLN downregulation could play an important role in abnormal intracellular Ca(2+) cycling in atrial pathology.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Animals
KW - Atrial Fibrillation
KW - Calcium
KW - Disease Models, Animal
KW - Down-Regulation
KW - Female
KW - Heart Atria
KW - Humans
KW - Ion Transport
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Middle Aged
KW - Muscle Proteins
KW - Proteolipids
KW - Sarcoplasmic Reticulum
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.bbrc.2011.05.113
DO - 10.1016/j.bbrc.2011.05.113
M3 - SCORING: Journal article
C2 - 21640081
VL - 410
SP - 97
EP - 101
JO - BIOCHEM BIOPH RES CO
JF - BIOCHEM BIOPH RES CO
SN - 0006-291X
IS - 1
ER -