Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Junctin is a transmembrane protein located at the cardiac junctional sarcoplasmic reticulum (SR) and forms a quaternary complex with the Ca(2+) release channel, triadin and calsequestrin. Impaired protein interactions within this complex may alter the Ca(2+) sensitivity of the Ca(2+) release channel and may lead to cardiac dysfunction, including hypertrophy, depressed contractility, and abnormal Ca(2+) transients. To study the expression of junctin and, for comparison, triadin, in heart failure, we measured the levels of these proteins in SR from normal and failing human hearts. Junctin was below our level of detection in SR membranes from failing human hearts, and triadin was downregulated by 22%. To better understand the role of junctin in the regulation of Ca(2+) homeostasis and contraction of cardiac myocytes, we used an adenoviral approach to overexpress junctin in isolated rat cardiac myocytes. A recombinant adenovirus encoding the green fluorescent protein served as a control. Infection of myocytes with the junctin-expressing virus resulted in an increased RNA and protein expression of junctin. Ca(2+) transients showed a decreased maximum Ca(2+) amplitude, and contractility of myocytes was depressed. Our results demonstrate that an increased expression of junctin is associated with an impaired Ca(2+) homeostasis. Downregulation of junctin in human heart failure may thus be a compensatory mechanism.
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PMID:On the role of junctin in cardiac Ca2+ handling, contractility, and heart failure. 1740 Jul 17

Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle. Within this complex, calsequestrin, triadin, and JCN appear to be critical for normal regulation of ryanodine receptor-mediated calcium (Ca) release. Junctin and triadin exhibit 60% to 70% amino acid homology in their transmembrane domains, including repeated KEKE motifs important for macromolecular protein-protein interactions within their SR luminal tails. Recent studies have uncovered functional roles of both JCN and triadin in the mouse heart, using transgenic overexpression strategies, which exhibit varying phenotypes including mild SR structural alterations, prolongation of Ca transient decay, impaired relaxation, and cardiac hypertrophy and/or heart failure. More specifically, both in vitro adenoviral gene transfer and in vivo gene-targeting techniques to manipulate JCN expression levels have shown that JCN is an essential factor in maintaining normal cardiac Ca handling and cardiac function. This article reviews the new findings on the regulatory roles of JCN in cardiac SR Ca cycling and contractility, with special emphasis on the effects of JCN ablation on delayed after depolarization-induced arrhythmias and premature mortality in mouse models.
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PMID:Regulatory roles of junctin in sarcoplasmic reticulum calcium cycling and myocardial function. 1820 2