title: Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c).
abstract: 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.
authors.affiliation: INSERM U689, IFR139, Hôpital Lariboisière, 8 Rue Guy Patin, 75475 Paris Cedex 10, France.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Dally
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bredoux
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Corvazier
authors.forename: Jens P
authors.initials: JP
authors.lastname: Andersen
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Clausen
authors.forename: Leonard
authors.initials: L
authors.lastname: Dode
authors.forename: Mohammed
authors.initials: M
authors.lastname: Fanchaouy
authors.forename: Pascal
authors.initials: P
authors.lastname: Gelebart
authors.forename: Virginie
authors.initials: V
authors.lastname: Monceau
authors.forename: Frederica
authors.initials: F
authors.lastname: Del Monte
authors.forename: Judith K
authors.initials: JK
authors.lastname: Gwathmey
authors.forename: Roger
authors.initials: R
authors.lastname: Hajjar
authors.forename: Chiraz
authors.initials: C
authors.lastname: Chaabane
authors.forename: Régis
authors.initials: R
authors.lastname: Bobe
authors.forename: Aly
authors.initials: A
authors.lastname: Raies
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Enouf
mesh_terms: D000328:Adult; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D009202:Cardiomyopathies / Q000201:enzymology* / Q000473:pathology*; D027682:Cation Transport Proteins; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology* / Q000473:pathology; D053499:Plasma Membrane Calcium-Transporting ATPases; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D027682:Cation Transport Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases