Alterations in necroptosis during ALDH2‑mediated protection against high glucose‑induced H9c2 cardiac cell injury.
Alterations in necroptosis during ALDH2‑mediated protection against high glucose‑induced H9c2 cardiac cell injury.
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ALDH2 介导的针对高葡萄糖诱导的 H9c2 心肌细胞损伤的保护过程中坏死性凋亡的变化
DOI：
10.3892/mmr.2018.9269
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发表时间：
2018-09
影响因子：
3.4
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Fang T;Cao R;Wang W;Ye H;Shen L;Li Z;Hu J;Gao Q
本研究的目的是探讨高糖（HG）诱导的H9c2心肌细胞损伤是否发生坏死性凋亡，以及乙醛脱氢酶2（ALDH2）的激活是否可以抑制坏死性凋亡。用35 mM葡萄糖处理H9c2心肌细胞，建立HG诱导的细胞损伤模型。 Alda-1 (20 µM)（一种 ALDH2 的特异性激活剂）和 necrostatin-1（Nec-1，100 µM）（一种坏死性凋亡抑制剂）用于在 HG 条件下处理 H9c2 心肌细胞。使用 Cell Counting Kit-8 测定法测量细胞活力，并通过二氢乙锭染色方法测量活性氧 (ROS) 的产生。 ALDH2 活性在 450 nm 处测量。通过逆转录定量聚合酶链反应和蛋白质印迹分析 ALDH2、坏死性凋亡相关基因、受体相互作用蛋白 (RIP)1、RIP3 和混合谱系激酶结构域如假激酶 (MLKL) 的 mRNA 和蛋白表达。还通过蛋白质印迹检查了裂解的 caspase-3 蛋白的表达。结果表明，在 HG 条件下，细胞活力、ALDH2 活性、mRNA 和蛋白表达均降低。此外，ROS 生成、RIP1、RIP3、MLKL 的 mRNA 和蛋白表达以及 cleaved caspase-3 的蛋白表达增加。 Alda-1 或 Nec-1 治疗可减弱 HG 诱导的 ALDH2 活性、mRNA 和蛋白质表达的下调。此外，RIP1、RIP3、MLKL mRNA 和蛋白表达下调。此外，Alda-1（而非 Nec-1）降低了 caspase-3 蛋白的表达。总的来说，这些数据表明 ALDH2 的激活可以保护 H9c2 心肌细胞免受 HG 诱导的损伤，部分是通过抑制坏死性凋亡的发生。
The aim of the present study was to investigate whether necroptosis occurs in high glucose (HG)-induced H9c2 cardiac cell injury and whether the activation of aldehyde dehydrogenase 2 (ALDH2) can inhibit necroptosis. H9c2 cardiac cells were treated with 35 mM glucose to establish a HG-induced cell injury model. Alda-1 (20 µM), a specific activator of ALDH2 and necrostatin-1 (Nec-1, 100 µM), an inhibitor of necroptosis were used to treat H9c2 cardiac cells under HG conditions. Cell viability was measured using a Cell Counting Kit-8 assay and reactive oxygen species (ROS) generation was measured by the dihydroethidium staining method. ALDH2 activity was measured at 450 nm. The mRNA and protein expression of ALDH2, necroptosis-associated genes, receptor-interacting protein (RIP)1, RIP3 and mixed lineage kinase domain like pseudokinase (MLKL), were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. The expression of cleaved caspase-3 protein was also examined by western blotting. The results demonstrated that under HG conditions, cell viability, ALDH2 activity, mRNA and protein expression were decreased. Furthermore, ROS generation, mRNA and protein expression of RIP1, RIP3, MLKL and the protein expression of cleaved caspase-3 were increased. Treatment with Alda-1 or Nec-1 attenuated HG-induced downregulation of ALDH2 activity, mRNA and protein expression. In addition, RIP1, RIP3, MLKL mRNA, and protein expression were downregulated. Furthermore, Alda-1 but not Nec-1 decreased cleaved caspase-3 protein expression. Collectively these data indicated that activation of ALDH2 protected H9c2 cardiac cells against HG-induced injury, partly by inhibiting the occurrence of necroptosis.
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影响因子：
--
作者：
Kang PF;Wu WJ;Tang Y;Xuan L;Guan SD;Tang B;Zhang H;Gao Q;Wang HJ
通讯作者：
Wang HJ
DOI：
10.1038/nrm3999
发表时间：
2015-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Fuchs Y;Steller H
通讯作者：
Steller H
影响因子：
56.9
作者：
Zhang, Duan-Wu;Shao, Jing;Han, Jiahuai
通讯作者：
Han, Jiahuai
线粒体乙醛脱氢酶 (ALDH2) 在 I 型糖尿病引起的心功能障碍中的新型保护机制：AMPK 调节的自噬的作用
DOI：
10.1016/j.bbadis.2014.05.017
发表时间：
2015-02-01
影响因子：
6.2
作者：
Guo, Yuli;Yu, Wenjun;Wang, Haichang
通讯作者：
Wang, Haichang
坏死性凋亡是一种新型的程序性细胞死亡，会导致成年小鼠脊髓损伤后的早期神经细胞损伤。
影响因子：
1.7
作者：
Liu, Ming;Wu, Wei;Hang, Chun-hua
通讯作者：
Hang, Chun-hua