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- Title
PLCδ1 Protein Rescues Ischemia-reperfused Heart by the Regulation of Calcium Homeostasis.
- Authors
Lim, Soyeon; Chang, Woochul; Cha, Min-Ji; Song, Byeong-Wook; Ham, Onju; Lee, Se-Yeon; Lee, Changyoun; Park, Jun-Hee; Lee, Sang-Kyou; Jang, Yangsoo; Hwang, Ki-Chul
- Abstract
Myocardial Ca2+ overload induced by ischemia/reperfusion (I/R) is a major element of myocardial dysfunction in heart failure. Phospholipase C (PLC) plays important roles in the regulation of the phosphoinositol pathway and Ca2+ homeostasis in various types of cells. Here, we investigated the protective role of PLCδ1 against myocardial I/R injury through the regulation of Ca2+ homeostasis. To investigate its role, PLCδ1 was fused to Hph1, a cell-permeable protein transduction domain (PTD), and treated into rat neonatal cardiomyocytes and rat hearts under respective hypoxia-reoxygenation (H/R) and ischemia-reperfusion conditions. Treatment with Hph1-PLCδ1 significantly inhibited intracellular Ca2+ overload, reactive oxygen species generation, mitochondrial permeability transition pore opening, and mitochondrial membrane potential elevation in H/R neonatal cardiomyocytes, resulting in the inhibition of apoptosis. Intravenous injections of Hph1-PLCδ1 in rats with I/R-injured myocardium caused significant reductions in infarct size and apoptosis and also improved systolic and diastolic cardiac functioning. Furthermore, a small ions profile obtained using time-of-flight secondary ion mass spectrometry showed that treatment with Hph1-PLCδ1 leads to significant recovery of calcium-related ions toward normal levels in I/R-injured myocardium. These results suggest that Hph1-PLCδ1 may manifest as a promising cardioprotective drug due to its inhibition of the mitochondrial apoptotic pathway in cells suffering from I/R injury.
- Subjects
CARDIAC contraction; HEART failure; PHOSPHOLIPASE C; ISCHEMIA; PHOSPHATIDYLINOSITOL 3-kinases
- Publication
Molecular Therapy, 2014, Vol 22, Issue 6, p1110
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.2014.46