Research Project
Grant-in-Aid for Scientific Research (C)
Ca^<2+> cycling via the sarcoplasmic reticulum (SR), an extensive intracellular membrane system of Ca^<2+> store, plays a critical role in maintaining normal cardiac function as well as in development of heart diseases. Cardiac SR Ca^<2+> ATPase (SERCA2a) primarily regulates the rate of Ca^<2+> re-uptake from the cytosole to the SR lumen during relaxation in the heart. A considerable number of studies have demonstrated that the decrease in SERCA2a activity is a common feature of heart failure and that restoring SERCA2a activity prevents the development of heart failure. Phospholamban is a main endogenous inhibitor that suppresses the activity of SERCA2a. Recent studies including ours have demonstrated that mutations in the phospholamban gene are associated with human cardiomyopathy. We found a heterozygous single nucleotide transitions of the SERCA2 gene in one patients with hypertrophic cardiomyopathy. Then, we generated transgenic mice harboring V540A mutant. In addition to phospholamban, a newly identified SR protein, sarcalumenin also regulate Ca^<2+> re-uptake through the interaction with SERCA2a. Sarcalumenin is a Ca^<2+> binding glycoprotein located in the lumen of the SR and thought to regulate Ca^<2+> transport and storage in the SR. Both SERCA2a mutant TG and sarcalumenin knockout mice exhibit mild relaxation-dominant cardiac dysfunction. Here we examined the effect of aging and pressure overload stresses on these mice. These stresses promoted cardiac dysfunction in sarcalumenin KO mice, and then indicated the important role of sarcalumenin-SERCA2a interaction in maintaining cardiac function.
All 2008 2007 2006 2005
All Journal Article (33 results) (of which Peer Reviewed: 17 results) Presentation (20 results)
Cardiovasc Res 77
Pages: 362-70
Cardiovasc Res 77(2)
Arch Dis Child Fetal Neonatal Ed. 93
J Biol Chem 283
Pages: 14335-44
Ped Res 62
Pages: 392-8
Physiol Genomics 31
Pages: 139-57
Am J Physiol Heart Circ Physiol 293
Am J Physilo Cell Physiol 293
Ped Res 62(4)
Physiol Genomics 31(1)
Am J Physiol Heart Cric Physiol 293(3)
Pages: 1662-72
Am J Physiol Cell Pkysiol 293(5)
Pages: 1498-508
Am J Physiol Cell Physiol 293
Clin Calcium 16
Pages: 37-44
FEBS letters 580
Pages: 2247-2252
J Cell Mol Med 10
Pages: 216-24
J Clin Invest 116
Pages: 3026-34
Am J Physiol Heart Circ Physiol 290(4)
Pages: 1660-70
Clin Calcium 16(1)
FEBS letters 580(9)
J Cell Mol Med 10(1)
J Clin Invest 116(11)
Pages: 216-224
Biochem Biophys Res Commun 334
Pages: 861-6
Am J Physiol Heart Circ Physiol 290
Biochem Biophys Res Commun 334(3)
