title: Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca2+ uptake in human atrial fibrillation.
abstract: 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.
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 165 South Orange Ave, MSB G609, Newark, NJ 07003, USA.
authors.forename: Mayilvahanan
authors.initials: M
authors.lastname: Shanmugam
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Molina
authors.forename: Shumin
authors.initials: S
authors.lastname: Gao
authors.forename: Renaud
authors.initials: R
authors.lastname: Severac-Bastide
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Fischmeister
authors.forename: Gopal J
authors.initials: GJ
authors.lastname: Babu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D011510:Proteolipids / Q000096:biosynthesis* / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin; D002118:Calcium