| First Author | Hong CS | Year | 2008 |
| Journal | J Mol Cell Cardiol | Volume | 44 |
| Issue | 4 | Pages | 672-82 |
| PubMed ID | 18353357 | Mgi Jnum | J:136077 |
| Mgi Id | MGI:3795058 | Doi | 10.1016/j.yjmcc.2008.01.012 |
| Citation | Hong CS, et al. (2008) Overexpression of junctate induces cardiac hypertrophy and arrhythmia via altered calcium handling. J Mol Cell Cardiol 44(4):672-82 |
| abstractText | Junctate-1 is a newly identified integral endoplasmic/sarcoplasmic reticulum Ca2+ binding protein. However, its functional role in the heart is unknown. In the present study, the consequences of constitutively overexpressed junctate in cardiomyocytes were investigated using transgenic (TG) mice overexpressing junctate-1. TG mice (8 weeks old) showed cardiac remodeling such as marked bi-atrial enlargement with intra-atrial thrombus and biventricular hypertrophy. The TG mice also showed bradycardia with atrial fibrillation, reduced amplitude and elongated decay time of Ca2+ transients, increased L-type Ca2+ current and prolonged action potential durations. Time-course study (2-8 weeks) showed an initially reduced SR function due to down-regulation of SERCA2 and calsequestrin followed by sarcolemmal protein expression and cardiac hypertrophy at later age. These sequential changes could well be correlated with the physiological changes. Adrenergic agonist treatment and subsequent biochemical study showed that junctate-1 TG mice (8 weeks old) were under local PKA signaling that could cause increased L-type Ca2+ current and reduced SR function. Junctate-1 in the heart is closely linked to the homeostasis of E-C coupling proteins and a sustained increase of junctate-1 expression leads to a severe cardiac remodeling and arrhythmias. |
