Sphingomyelin synthase 2 (SMS2) is a vital contributor to tissue injury and affects various pathological processes. However, whether SMS2 participates in the modulation of cardiac injury in myocardial infarction has not been determined. This study aimed to evaluate the potential role of SMS2 in the regulation of cardiomyocyte injury induced by hypoxia, an in vitro model for studying myocardial infarction. Our data revealed that SMS2 expression was significantly upregulated in cardiomyocytes in response to hypoxia. Loss-of-function experiments revealed that knockdown of SMS2 markedly restored the viability of cardiomyocytes impaired by hypoxia, and attenuated hypoxia-evoked apoptosis and reactive oxygen species (ROS) generation. In contrast, cardiomyocytes that highly expressed SMS2 were more sensitive to hypoxia-induced injury. Moreover, SMS2 deficiency enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling through inactivation of glycogen synthase kinase-3β. Notably, suppression of Nrf2 markedly abrogated SMS2 knockdown-mediated cardioprotective effects on hypoxia-exposed cardiomyocytes. Our results illustrate that downregulation of SMS2 exerts a cardioprotective function by protecting cardiomyocytes from hypoxia-induced apoptosis and oxidative stress through enhancement of Nrf2 activation. Our study indicates a potential role of SMS2 in the modulation of cardiac injury, which may contribute to the progression of myocardial infarction.

鞘磷脂合酶 2 (SMS2) 是组织损伤的重要因素，并影响各种病理过程。然而，SMS2是否参与了心肌梗塞心脏损伤的调节尚未确定。本研究旨在评估 SMS2 在调节缺氧诱导的心肌细胞损伤中的潜在作用，这是一种用于研究心肌梗塞的体外模型。我们的数据显示，SMS2 表达在心肌细胞中显着上调以响应缺氧。功能丧失实验表明，SMS2 的敲低显着恢复了缺氧受损的心肌细胞的活力，并减弱了缺氧引起的细胞凋亡和活性氧 (ROS) 的产生。相比之下，高表达 SMS2 的心肌细胞对缺氧诱导的损伤更敏感。而且，SMS2 缺乏通过糖原合酶激酶 3β 的失活增强了核因子红细胞 2 相关因子 2 (Nrf2) 信号的激活。值得注意的是，抑制 Nrf2 显着消除了 SMS2 敲低介导的对缺氧暴露心肌细胞的心脏保护作用。我们的结果表明，SMS2 的下调通过增强 Nrf2 活化来保护心肌细胞免受缺氧诱导的细胞凋亡和氧化应激，从而发挥心脏保护功能。我们的研究表明 SMS2 在调节心脏损伤中的潜在作用，这可能有助于心肌梗塞的进展。抑制 Nrf2 显着消除了 SMS2 敲低介导的对缺氧暴露心肌细胞的心脏保护作用。我们的结果表明，SMS2 的下调通过增强 Nrf2 活化来保护心肌细胞免受缺氧诱导的细胞凋亡和氧化应激，从而发挥心脏保护功能。我们的研究表明 SMS2 在调节心脏损伤中的潜在作用，这可能有助于心肌梗塞的进展。抑制 Nrf2 显着消除了 SMS2 敲低介导的对缺氧暴露心肌细胞的心脏保护作用。我们的结果表明，SMS2 的下调通过增强 Nrf2 活化来保护心肌细胞免受缺氧诱导的细胞凋亡和氧化应激，从而发挥心脏保护功能。我们的研究表明 SMS2 在调节心脏损伤中的潜在作用，这可能有助于心肌梗塞的进展。