Abstract
Ischemia followed by blood supply reperfusion in cardiomyocytes leads to an overproduction of free radicals and a rapid decrease of adenosine triphosphate concentration. The cardioprotective effect of a potential drug, adenine, was evaluated using H9c2 rat cardiomyoblasts. After hypoxia–reoxygenation (HR) treatment consisting of hypoxia for 21 h followed by reoxygenation for 6 h, it was revealed that pretreatment with 200 µM adenine for 2 h effectively prevented HR-induced cell death. Adenine also significantly decreased the production of reactive oxygen species and reduced cell apoptosis after HR injury. The antioxidant effect of adenine was also revealed in this study. Adenine pretreatment significantly reduced the expression of activating transcription factor 4 (ATF4) and glucose-regulated protein 78 (GRP78) proteins, and protein disulfide isomerase induced a protective effect on mitochondria after HR stimulation. Intracellular adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor delta (PPARδ), and perilipin levels were increased by adenine after HR stimulation. Adenine had a protective effect in HR-damaged H9c2 cells. It may be used in multiple preventive medicines in the future.
Highlights
Coronary artery disease is a major cause of mortality and disability in most countries in the world
Water-soluble tetrazolium salt (WST)-1 analysis demonstrated that HR significantly decreased cell viability, and pretreatment with adenine for 2 h before HR significantly reduced HR-induced cell death (Figure 1C)
This study showed that hypoxia–reoxygenation (HR) injury in cardiomyocytes induced ROS production, cell apoptosis, and endoplasmic reticulum (ER) stress, which may be attenuated by pretreatment with adenine
Summary
Coronary artery disease is a major cause of mortality and disability in most countries in the world. Obstruction of coronary artery results in ischemic myocardial injury and permanent cell death [1]. Compared to permanent coronary artery obstruction, reperfusion of blood flow after reperfusion therapy causes additional cell damage and death after ischemia, referred to as myocardial ischemia-reperfusion injury [3]. The increased oxidative stress coupled with pH restoration induce the opening of the mitochondrial permeability transition pore [6]. This large, nonspecific pore allows passage between the mitochondrial matrix and the cytosol, which disrupts the normally finely regulated transport of protons and ions and leads to swelling and rupture of the mitochondria, which triggers necrotic cell death [7]
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