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Acute myocardial infarction is regarded as myocardial necrosis resulting from myocardial ischemia/reperfusion (I/R) damage and retains a major cause of mortality. Neferine, which was extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., has been reported to possess a broad range of biological activities. However, its underlying mechanism on the protective effect of I/R has not been fully clarified. A hypoxia/reoxygenation (H/R) model with H9c2 cells closely simulating myocardial I/R injury was used as a cellular model. This study intended to research the effects and mechanism underlying neferine on H9c2 cells in response to H/R stimulation. Cell Counting Kit‐8 and lactate dehydrogenase (LDH) release assays were employed to measure cell viability and LDH, respectively. Apoptosis and reactive oxygen species (ROS) were determined by flow cytometry analysis. Oxidative stress was evaluated by detecting malondialdehyde, superoxide dismutase, and catalase. Mitochondrial function was assessed by mitochondrial membrane potential, ATP content, and mitochondrial ROS. Western blot analysis was performed to examine the expression of related proteins. The results showed that hypoxia/reoxygenation (H/R)‐induced cell damage, all of which were distinctly reversed by neferine. Moreover, we observed that neferine inhibited oxidative stress and mitochondrial dysfunction induced by H/R in H9c2 that were concomitant with increased sirtuin‐1 (SITR1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and heme oxygenase‐1 expression. On the contrary, silencing the SIRT1 gene with its small interferingRNA eliminated the beneficial effects of neferine. It is concluded that neferine preconditioning attenuated H/R‐induced cardiac damage via suppressing apoptosis, oxidative stress, and mitochondrial dysfunction, which may be partially ascribed to the activation of SIRT1/Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

Echinacoside (ECH) is a compound derived from the natural herbs Cistanche and Echinacea, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe2+ and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence Gpx4. In vitro and in vivo, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of Gpx4 inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF. [ABSTRACT FROM AUTHOR]

TUG1 has been reported to play an important role in various cancer types. However, the study about the function of lncRNA TUG1 in myocardial infarction is limited. This study was aimed to investigate the role of TUG1 in H9c2 cell injury induced by hypoxia and explore its possible molecular mechanism. The proliferation assay, migration assay, invasion assay, and apoptosis assay were performed. RT-PCR was used to determine the relative RNA expression of TUG1, miR-124 and Hic-5. Western blotting was used to detect the expression levels of apoptotic proteins, Hic-5, Sp1, and Survivin. Hypoxia could significantly decrease cell proliferation, migration and invasion and increase H9c2 cell apoptosis. Knock-down of TUG1 promoted the cell damage induced by hypoxia. miR-124 was the direct target of TUG1 and down-regulated by TUG1. TUG1 silence aggravated hypoxia injury by up-regulating miR-124. In addition, Hic-5 was the target of miR-124 and negatively regulated by miR-124. Our findings showed that Hic-5 over-expression could significantly induce increases in cell viability, migration and invasion, and induce decrease in cell apoptosis after hypoxia damage. Over-expression of Hic-5 could increase the expression of Sp1 and Survivin, which inhibited the cell apoptosis, thereby reducing the cell damage induced by hypoxia. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the leading causes of death. Wilms' tumor 1-associating protein (WTAP), one of the components of the m 6 A methyltransferase complex, has been shown to affect gene expression via regulating mRNA modification. Although WTAP has been implicated in various diseases, its role in MI is unclear. In this study, we found that hypoxia/reoxygenation (H/R) time-dependently increased WTAP expression, which in turn promoted endoplasmic reticulum (ER) stress and apoptosis, in human cardiomyocytes (AC16). H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA. We then investigated the underlying molecular mechanism and found that WTAP affected m 6 A methylation of ATF4 mRNA to regulate its expression, and that the inhibitory effects of WTAP on ER stress and apoptosis were ATF4 dependent. Finally, WTAP's effects on myocardial I/R injury were confirmed in vivo . WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m 6 A modification of ATF4 mRNA. These findings highlight the importance of WTAP in I/R injury and provide new insights into therapeutic strategies for MI.