Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Aging (Albany NY). 2021 Sep 24;13(18):22444-22458. doi: 10.18632/aging.203551.
Suppressor of variegation 3-9 homolog 2 (SUV39H2/KMT1B), a member of the SUV39 subfamily of lysine methyltransferases (KMTs), functions as an oncogene in various types of cancers. Here, we demonstrate a novel function of SUV39H2 that drives the cardiomyocyte aging process through BTG2. In our study, cardiomyocyte aging was induced by H2O2 and aging cells exhibited increases in SUV39H2. Knockdown of SUV39H2 accelerated cardiomyocyte senescence, while overexpression of SUV39H2 inhibited the cardiomyocyte senescence phenotype. These effects of SUV39H2 on cardiomyocytes were independent of DNA damage and mitochondrial dysfunction. Interestingly, RNA sequencing and bioinformatics analyses identified a strong correlation between SUV39H2 and BTG2. In addition to this, BTG2 protein levels were significantly increased in SUV39H2-deficient cardiomyocytes, and BTG2 knockdown virtually rescued the cardiomyocyte senescence phenotype induced by SUV39H2 knockdown. Taken together, these results indicate that SUV39H2 protects cardiomyocytes from H2O2 exposure-induced oxidative stress, DNA damage, and mitochondrial dysfunction by regulating the p53-BTG2 pathway. Our findings provide evidence that the activation of SUV39H2 has therapeutic or preventive potential against cardiac aging.
抑制杂色 3-9 同源物 2（SUV39H2/KMT1B）是赖氨酸甲基转移酶（KMTs）SUV39 亚家族的成员，作为一种癌基因在多种类型的癌症中发挥作用。在这里，我们证明了 SUV39H2 的一个新功能，它通过 BTG2 驱动心肌细胞衰老过程。在我们的研究中，通过 H2O2 诱导心肌细胞衰老，衰老细胞中 SUV39H2 增加。SUV39H2 的敲低加速了心肌细胞衰老，而过表达 SUV39H2 抑制了心肌细胞衰老表型。SUV39H2 对心肌细胞的这些影响不依赖于 DNA 损伤和线粒体功能障碍。有趣的是，RNA 测序和生物信息学分析表明 SUV39H2 与 BTG2 之间存在很强的相关性。除此之外，在 SUV39H2 缺陷型心肌细胞中，BTG2 蛋白水平显著增加，而 BTG2 的敲低几乎挽救了 SUV39H2 敲低诱导的心肌细胞衰老表型。总之，这些结果表明 SUV39H2 通过调节 p53-BTG2 通路来保护心肌细胞免受 H2O2 暴露引起的氧化应激、DNA 损伤和线粒体功能障碍。我们的研究结果为 SUV39H2 的激活在对抗心脏衰老方面具有治疗或预防潜力提供了证据。
