title: SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in children with congenital heart defects.
abstract: In animal models of conotruncal heart defects, an abnormal calcium sensitivity of the contractile apparatus and a depressed L-type calcium current have been described. Sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) is a membrane protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to the SR. The activity of SERCA is inhibited by phospholamban (PLN) and sarcolipin (SLN), and all these proteins participate in maintaining the normal intracellular calcium handling. Ryanodine receptors (RyRs) are the major SR calcium-release channels required for excitation-contraction coupling in skeletal and cardiac muscle. Our objective was to evaluate SERCA2a (i.e., the SERCA cardiac isoform), PLN, SLN, and RyR2 (i.e., the RyR isoform enriched in the heart) gene expression in myocardial tissue of patients affected by tetralogy of Fallot (TOF), a conotruncal heart defect. The gene expression of target genes was assessed semiquantitatively by RT-PCR using the calsequestrin (CASQ, a housekeeping gene) RNA as internal standard in the atrial myocardium of 23 pediatric patients undergoing surgical correction of TOF, in 10 age-matched patients with ventricular septal defect (VSD) and in 13 age-matched children with atrial septal defect (ASD). We observed a significantly lower expression of PLN and SLN in TOF patients, while there was no difference between the expression of SERCA2a and RyR2 in TOF and VSD. These data suggest a complex mechanism aimed to enhance the intracellular Ca(2+) reserve in children affected by tetralogy of Fallot.
authors.affiliation: Molecular Cardiology and Genetics Laboratory, Institute of Clinical Physiology, National Research Council, G Pasquinucci Hospital, Massa, Italy. simona.vittorini@ifc.cnr.it
authors.forename: Simona
authors.initials: S
authors.lastname: Vittorini
authors.forename: Simona
authors.initials: S
authors.lastname: Storti
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Parri
authors.forename: Alfredo Giuseppe
authors.initials: AG
authors.lastname: Cerillo
authors.forename: Aldo
authors.initials: A
authors.lastname: Clerico
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D009124:Muscle Proteins; D011510:Proteolipids; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C077258:sarcolipin; C506946:ATP2A2 protein, human