SOD2
化学
自噬
活性氧
氧化应激
HDAC6型
组蛋白脱乙酰酶抑制剂
药理学
心力衰竭
组蛋白脱乙酰基酶
血红素加氧酶
超氧化物歧化酶
内分泌学
内科学
医学
生物化学
组蛋白
细胞凋亡
血红素
酶
基因
作者
Tianwei Cheng,Chang Liu,Yufei Wang,Liang Yang,Lifeng Feng,Shengzheng Zhang,Bing Qi,Jianlin Cui,Lihong Guo,Lei Cao,Yanming Wang,Zhi Qi,Liang Yang
标识
DOI:10.1016/j.taap.2024.116957
摘要
Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Se-SAHA significantly attenuated the generation of ISO-induced reactive oxygen species (ROS) and restored the expression levels of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) in vitro. Furthermore, Se-SAHA pretreatment prevented the accumulation of autophagosomes. Se-SAHA reversed the high expression of HDAC1 and HDAC6 induced by ISO incubation. However, after the addition of the HDAC agonist, the effect of Se-SAHA on blocking autophagy was inhibited. Using ISO-induced mouse models, cardiac ventricular contractile dysfunction, hypertrophy, and fibrosis was reduced treated by Se-SAHA. In addition, Se-SAHA inhibited HDAC1 and HDAC6 overexpression in ISO-treated mice. Se-SAHA treatment significantly increased the activity of SOD2 and improved the ability to eliminate free radicals. Se-SAHA hindered the excessive levels of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 in heart failure mice. Collectively, our results indicate that Se-SAHA exerts cardio-protection against ISO-induced heart failure via antioxidative stress and autophagy inhibition.
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