Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun 130021, Jilin, China.
Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, Jilin, China.
Aging (Albany NY). 2022 Aug 23;14(16):6740-6755. doi: 10.18632/aging.204247.
Oxidative stress is the central cause of angiotensin II (Ang II)-induced myocardial injury, and nuclear factor erythroid 2-related factor (Nrf2) is the core molecule of the anti-oxidant defense system. We have previously demonstrated that sulforaphane (SFN) can prevent Ang II-induced myocardial injury by activating Nrf2; however, the underlying molecular mechanism is still unclear. This study aimed to evaluate whether SFN prevents Ang II-induced cardiomyocyte apoptosis through acetylation modification of . Wild-type and knockdown embryonic rat cardiomyocytes (H9C2) were exposed to Ang II to induce apoptosis, oxidative stress, and inflammatory responses. SFN treatment significantly reduced Ang II-induced cardiomyocyte apoptosis, inflammation and oxidative stress. Activation of Nrf2 played a critical role in preventing cardiomyocyte apoptosis. After Nrf2 was knockdown, the anti-inflammatory, antioxidant stress of SFN were eliminated. Furthermore, Nrf2 activation by SFN was closely related to the decreased activity of histone deacetylases (HDACs) and increased histone-3 (H3) acetylation levels in promoter region. These findings confirm that Nrf2 plays a key role in SFN preventing Ang II-induced cardiomyocyte apoptosis. SFN activates Nrf2 by inhibiting HDACs expression and activation.
氧化应激是血管紧张素 II（Ang II）诱导心肌损伤的核心原因，核因子红细胞 2 相关因子（Nrf2）是抗氧化防御系统的核心分子。我们之前已经证明，萝卜硫素（SFN）可以通过激活 Nrf2 来预防 Ang II 诱导的心肌损伤；然而，其潜在的分子机制尚不清楚。本研究旨在评估 SFN 是否通过 的乙酰化修饰来预防 Ang II 诱导的心肌细胞凋亡。野生型和 敲低的胚胎大鼠心肌细胞（H9C2）暴露于 Ang II 中以诱导细胞凋亡、氧化应激和炎症反应。SFN 处理显著减少了 Ang II 诱导的心肌细胞凋亡、炎症和氧化应激。Nrf2 的激活在预防心肌细胞凋亡中起着关键作用。Nrf2 被敲低后，SFN 的抗炎、抗氧化应激作用被消除。此外，SFN 通过抑制组蛋白去乙酰化酶（HDACs）的活性和增加组蛋白-3（H3）在 启动子区域的乙酰化水平来激活 Nrf2。这些发现证实了 Nrf2 在 SFN 预防 Ang II 诱导的心肌细胞凋亡中起着关键作用。SFN 通过抑制 HDACs 的表达和激活来激活 Nrf2。
