Abstract
Polydatin (PD), a monocrystalline polyphenolic drug mainly found in the roots of Polygonum cuspidatum, has various pharmacological activities. Long non-coding RNAs (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) was found to participate in the suppression of multiple cancers. Here, we proposed to study the effect of PD on myocardial infarction (MI) by inducing DGCR5. CCK-8 assay was performed to detect the viability of H9c2 cells. Flow cytometry was utilized to test apoptosis of H9c2 cells. These results determined the optimal concentration and effect time of hypoxia as well as PD. Si-DGCR5 was transfected into cells and the expression level was determined by qRT-PCR. Western blot was utilized to evaluate the expression of apoptosis-related proteins, Bcl-2, Bax, and cleaved-caspase-3, as well as autophagy-associated proteins including Beclin-1, p62, and LC3-II/LC3-I. As a result, PD efficiently attenuated hypoxia-induced apoptosis and autophagy in H9c2 cells. The expression of DGCR5 was down-regulated by hypoxia and up-regulated by PD. Besides, knocking-down the expression of DGCR5 inhibited the protection of PD in H9c2 cells. In addition, PD up-regulated the accumulation of DGCR5, DGCR5 decreased the expression of Bcl-2 and p62, raised the expression of Bax and cleaved-caspase-3, and the proportion of LC3-II/LC3-I. PD stimulated the PI3K/AKT/mTOR and MEK/ERK signaling pathways via up-regulating the expression of DGCR5. Our data demonstrated that PD reduced cell apoptosis and autophagy induced by hypoxia in cardiomyocytes. Moreover, PD activated PI3K/AKT/mTOR and MEK/ERK signaling pathways by up-regulating the expression of DGCR5.
Highlights
Myocardial infarction (MI) is a prevalent clinical manifestation for ischemic heart disease and coronary artery disease [1]
Hypoxic injury was induced in H9c2 cells To investigate the effect of hypoxia, H9c2 cells were treated in hypoxia for 0, 2, 4, 8, 16, and 24 h
The expression of Beclin-1 was increased (P=0.0002), the expression of p62 was decreased (P=0.0002), and the expression of LC-3 II/LC-3 I was increased (P=0.0001, Figure 1E and F). These results implied that hypoxia could induce apoptosis and autophagy in H9c2 cells
Summary
Myocardial infarction (MI) is a prevalent clinical manifestation for ischemic heart disease and coronary artery disease [1]. 3–4 million people have an MI annually [2]. The manifestations of MI are varying degrees of chest pain, which can move to the left arm or left side of the neck, dyspnea, sweating, nausea, irregular heartbeat, apprehension, fatigue, etc. The current treatment of MI is taking drugs that act to lower blood cholesterol and platelet aggregation, such as aspirin and tissue plasminogen activator (tPA). Several painkillers are recommended to relieve the pain associated with MI, such as morphine and meperidine [4]. One million deaths are caused by MI annually [5]. Comprehensive research on prevention and treatment of MI is still necessary
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