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Protective effect of dimethyl fumarate on oxidative damage and signaling in cardiomyocytes.
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2020-07-15 , DOI: 10.3892/mmr.2020.11342 Yuanyuan Kuang 1 , Yinzhuang Zhang 2 , Zhen Xiao 1 , Lijun Xu 1 , Ping Wang 1 , Qilin Ma 1
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2020-07-15 , DOI: 10.3892/mmr.2020.11342 Yuanyuan Kuang 1 , Yinzhuang Zhang 2 , Zhen Xiao 1 , Lijun Xu 1 , Ping Wang 1 , Qilin Ma 1
Affiliation
Myocardial ischemia/reperfusion (I/R) injury contributes to the pathogenesis of numerous diseases. Based on its antioxidant and anti‑inflammatory effects, dimethyl fumarate (DMF) has been reported to exert protective effects against I/R. However, to the best of our knowledge, its potential role as a myocardial protective agent in heart disease has received little attention. Previous studies have suggested that DMF may exert its protective effects by activating nuclear factor erythroid 2‑related factor 2 (Nrf2); however, the exact underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the protective role of DMF in myocardial I/R injury, and to determine the role of Nrf2 in mediating the activity of DMF. H9c2 cells were incubated with DMF (20 µM) for 24 h before establishing the I/R model, and were then subjected to myocardial ischemia for 6 h, followed by reperfusion. Cell viability, lactate dehydrogenase levels, anti‑oxidant enzyme expression levels and anti‑apoptotic effects were evaluated, and AKT/Nrf2 pathway‑associated mechanisms were investigated. The results of the present study indicated that DMF may reduce myocardial I/R injury in a Nrf2‑dependent manner. DMF significantly improved cellular viability, suppressed the expression of apoptotic markers, decreased the production of reactive oxygen species and increased the expression of Nrf2‑regulated antioxidative genes. Notably, these beneficial DMF‑mediated effects were not observed in the control or I/R groups. In conclusion, the results of the present study suggested that DMF may exert protective effects against a myocardial I/R model, and further validated Nrf2 modulation as a primary mode of action. Thus suggesting that DMF may be a potential therapeutic agent for AKT/Nrf2 pathway activation in myocardial, and potentially systemic, diseases.
中文翻译:
富马酸二甲酯对心肌细胞氧化损伤和信号传导的保护作用。
心肌缺血/再灌注(I/R)损伤是多种疾病的发病机制之一。据报道,富马酸二甲酯 (DMF) 具有抗氧化和抗炎作用,可对 I/R 发挥保护作用。然而,据我们所知,其作为心肌保护剂在心脏病中的潜在作用很少受到关注。此前的研究表明,DMF可能通过激活核因子红细胞2相关因子2(Nrf2)发挥其保护作用;然而,确切的潜在机制仍有待阐明。本研究的目的是探讨DMF在心肌I/R损伤中的保护作用,并确定Nrf2在介导DMF活性中的作用。 H9c2细胞在建立I/R模型之前用DMF(20μM)孵育24小时,然后进行心肌缺血6小时,然后再灌注。评估了细胞活力、乳酸脱氢酶水平、抗氧化酶表达水平和抗凋亡作用,并研究了 AKT/Nrf2 通路相关机制。本研究的结果表明,DMF 可能以 Nrf2 依赖性方式减轻心肌 I/R 损伤。 DMF 显着提高细胞活力,抑制凋亡标记物的表达,减少活性氧的产生并增加 Nrf2 调节的抗氧化基因的表达。值得注意的是,这些有益的 DMF 介导的作用在对照组或 I/R 组中没有观察到。总之,本研究的结果表明DMF可能对心肌I/R模型发挥保护作用,并进一步验证了Nrf2调节作为主要作用模式。 因此表明 DMF 可能是心肌疾病和潜在全身疾病中 AKT/Nrf2 通路激活的潜在治疗剂。
更新日期:2020-09-21
中文翻译:
富马酸二甲酯对心肌细胞氧化损伤和信号传导的保护作用。
心肌缺血/再灌注(I/R)损伤是多种疾病的发病机制之一。据报道,富马酸二甲酯 (DMF) 具有抗氧化和抗炎作用,可对 I/R 发挥保护作用。然而,据我们所知,其作为心肌保护剂在心脏病中的潜在作用很少受到关注。此前的研究表明,DMF可能通过激活核因子红细胞2相关因子2(Nrf2)发挥其保护作用;然而,确切的潜在机制仍有待阐明。本研究的目的是探讨DMF在心肌I/R损伤中的保护作用,并确定Nrf2在介导DMF活性中的作用。 H9c2细胞在建立I/R模型之前用DMF(20μM)孵育24小时,然后进行心肌缺血6小时,然后再灌注。评估了细胞活力、乳酸脱氢酶水平、抗氧化酶表达水平和抗凋亡作用,并研究了 AKT/Nrf2 通路相关机制。本研究的结果表明,DMF 可能以 Nrf2 依赖性方式减轻心肌 I/R 损伤。 DMF 显着提高细胞活力,抑制凋亡标记物的表达,减少活性氧的产生并增加 Nrf2 调节的抗氧化基因的表达。值得注意的是,这些有益的 DMF 介导的作用在对照组或 I/R 组中没有观察到。总之,本研究的结果表明DMF可能对心肌I/R模型发挥保护作用,并进一步验证了Nrf2调节作为主要作用模式。 因此表明 DMF 可能是心肌疾病和潜在全身疾病中 AKT/Nrf2 通路激活的潜在治疗剂。