1. iPLA 2 β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury.
- Author
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Jin T, Lin J, Gong Y, Bi X, Hu S, Lv Q, Chen J, Li X, Chen J, Zhang W, Wang M, and Fu G
- Subjects
- Animals, Animals, Newborn, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Primary Cell Culture, Rats, Sprague-Dawley, Rats, Group VI Phospholipases A2 physiology, Myocardial Infarction metabolism, Myocardial Infarction pathology, Myocardial Reperfusion Injury metabolism, Myocardial Reperfusion Injury pathology, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology
- Abstract
Both calcium-independent phospholipase A2 beta (iPLA
2 β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2 β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2 β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2 β knockout mice and siRNA mediated iPLA2 β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2 β. Our data demonstrate the increase of iPLA2 β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2 β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2 β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2 β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.- Published
- 2021
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