The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) actively transports into the sarcoplasmic to facilitate cardiac muscle relaxation. Phospholamban (PLN) allosterically inhibits SERCA, and an imbalance of SERCA2a, dominant isoform, PLN content disrupts homeostasis contractility. A previous study has shown that ovariectomized (OVX) rats have reduced SERCA activity due lowered SERCA2a increased...

Dilated cardiomyopathy and end-stage heart failure result in multiple defects in cardiac excitation-contraction coupling. Via complementation of a genetically based mouse model of dilated cardiomyopathy, we now provide evidence that progressive chamber dilation and heart failure are dependent on a Ca2+ cycling defect in the cardiac sarcoplasmic reticulum. The ablation of a muscle-specific sarco...

The relative mRNA levels corresponding to the different sarcoplasmic/endoplasmic-reticulum Ca(2+)-ATPase isoforms (SERCA1a, SERCA1b, SERCA2a, SERCA2b and SERCA3) were measured by reverse transcriptase-PCR in rat soleus muscles regenerating after notexin-induced necrosis. The succession of appearance of the different types of SERCA mRNA species in regenerating muscle largely recapitulates those ...

Phospholamban, the critical regulator of the cardiac SERCA2a Ca affinity, is phosphorylated at Ser and Thr during -adrenergic stimulation (eg, isoproterenol). To assess the impact of nonphosphorylatable phospholamban, a S16A, T17A double-mutant (DM) was introduced into phospholamban knockout mouse hearts. Transgenic lines expressing DM phospholamban at levels similar to wild types (WT) were ide...

Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiom...

Taurine is a beta-amino acid found in very high concentration in the heart. Depletion of these intracellular stores results in the development of cardiomyopathy, thought to be mediated by abnormal sarcoplasmic reticular (SR) Ca(2+) transport. There is also evidence that taurine directly alters the Ca(2+) sensitivity of myofibrillar proteins. Major regulators of SR Ca(2+) ATPase (SERCA2a) are th...

Phytoestrogens are naturally occurring estrogenic compounds found in plants and plant products. These compounds are also known to exert cellular effects independent of their interactions with estrogen receptors. We studied the effects of the phytoestrogens phloretin, phloridzin, genistein, and biochanin A on Ca(2+) uptake into the cardiac muscle sarcoplasmic reticulum (SR). Genistein and biocha...

BACKGROUND Hspa1a and Hspa1b genes encode stress-inducible 70-kDa heat shock proteins (Hsp70) that protect cells from insults such as ischemia. Mice with null mutations of both genes (KO) were generated, and their cardiac phenotype was explored. METHODS AND RESULTS Heart rate and blood pressures were normal in the KO mice. Hearts from KO mice were more susceptible to both functional and cellu...

OBJECTIVES Expression of the cardiac Na(+)-Ca2+ exchanger (NCX) is high at birth and declines rapidly to adult levels by approximately 21 days in rabbits. The aim was to evaluate the role of thyroid hormone in regulating cardiac NCX expression. METHODS Adult New Zealand White rabbits were made hypothyroid by treatment with propylthiouracil or hyperthryoid by administration of sigma-thyroxine....