Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c)
Autor: | Virginie Monceau, Regis Bobe, Judith K. Gwathmey, Elisabeth Corvazier, Jocelyne Enouf, Aly Raies, Jens Peter Andersen, Johannes D. Clausen, Roger J. Hajjar, Raymonde Bredoux, Leonard Dode, Chiraz Chaabane, Saoussen Dally, Frederica Del Monte, Mohammed Fanchaouy, Pascal Gélébart |
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Rok vydání: | 2006 |
Předmět: |
Adult
Gene isoform medicine.medical_specialty SERCA Gene Expression Calcium-Transporting ATPases Biology Endoplasmic Reticulum Biochemistry Cell Line Sarcoplasmic Reticulum Calcium-Transporting ATPases Plasma Membrane Calcium-Transporting ATPases Internal medicine Idiopathic dilated cardiomyopathy Gene expression medicine Humans Protein Isoforms Calcium Signaling RNA Messenger Cation Transport Proteins Molecular Biology Sarcolemma Gene Expression Profiling Myocardium Endoplasmic reticulum Membrane Proteins Cell Biology Middle Aged Recombinant Proteins Cell biology Sarcoplasmic Reticulum Endocrinology Gene Expression Regulation Microsome Heterologous expression Cardiomyopathies Research Article |
Zdroj: | Aarhus University |
ISSN: | 1470-8728 0264-6021 |
Popis: | We recently documented the expression of a novel human mRNA variant encoding a yet uncharacterized SERCA [SR (sarcoplasmic reticulum)/ER (endoplasmic reticulum) Ca2+-ATPase] protein, SERCA2c [Gélébart, Martin, Enouf and Papp (2003) Biochem. Biophys. Res. Commun. 303, 676–684]. In the present study, we have analysed the expression and functional characteristics of SERCA2c relative to SERCA2a and SERCA2b isoforms upon their stable heterologous expression in HEK-293 cells (human embryonic kidney 293 cells). All SERCA2 proteins induced an increased Ca2+ content in the ER of intact transfected cells. In microsomes prepared from transfected cells, SERCA2c showed a lower apparent affinity for cytosolic Ca2+ than SERCA2a and a catalytic turnover rate similar to SERCA2b. We further demonstrated the expression of the endogenous SERCA2c protein in protein lysates isolated from heart left ventricles using a newly generated SERCA2c-specific antibody. Relative to the known uniform distribution of SERCA2a and SERCA2b in cardiomyocytes of the left ventricle tissue, SERCA2c was only detected in a confined area of cardiomyocytes, in close proximity to the sarcolemma. This finding led us to explore the expression of the presently known cardiac Ca2+-ATPase isoforms in heart failure. Comparative expression of SERCAs and PMCAs (plasma-membrane Ca2+-ATPases) was performed in four nonfailing hearts and five failing hearts displaying mixed cardiomyopathy and idiopathic dilated cardiomyopathies. Relative to normal subjects, cardiomyopathic patients express more PMCAs than SERCA2 proteins. Interestingly, SERCA2c expression was significantly increased (166±26%) in one patient. Taken together, these results demonstrate the expression of the novel SERCA2c isoform in the heart and may point to a still unrecognized role of PMCAs in cardiomyopathies. |
Databáze: | OpenAIRE |
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