MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53-dependent apoptosis pathway in N2a neuroblastoma cells.
MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53-dependent apoptosis pathway in N2a neuroblastoma cells.
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MicroRNA-29b 通过抑制 N2a 神经母细胞瘤细胞中 p53 依赖性凋亡途径减轻氧和葡萄糖剥夺/再灌注引起的损伤
DOI：
10.3892/etm.2017.5410
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Zhou S
中科院分区：
文献类型：
--
作者：
Cao L;Zhang Y;Zhang S;Jiang TP;Chen L;Liu J;Zhou S
脑缺血损伤引起严重的脑损伤，仍然是世界范围内发病率和死亡率的主要原因之一。microRNA-29 （miR-29）家族成员参与了脑缺血的调节过程，可能成为诊断和治疗脑缺血的生物标志物。miR-29b在脑缺血损伤中的作用尚不清楚。本研究的目的是研究miR-29b过表达是否抑制脑缺血损伤，并探讨其潜在的作用机制。结果表明，在氧和葡萄糖剥夺/再灌注（OGD/R）治疗后，N2a神经母细胞瘤细胞中miR-29b水平下降。在OGD/ r处理的N2a细胞中，转染miR-29b模拟物可显著提高细胞活力，减少乳酸脱氢酶（LDH）渗漏，通过减少细胞核形态学变化和降低caspase-3活性来抑制细胞凋亡。相反，miR-29b抑制剂增强了OGD/ r诱导的细胞毒性和细胞凋亡。此外，在OGD/R处理的N2a细胞中，miR-29b模拟物阻断了Bax和p53表达的增加，并降低了Bcl-2表达，而miR-29b抑制剂则加剧了OGD/R引起的这些凋亡相关蛋白的表达变化。使用p53小干扰RNA敲低p53可降低细胞活力，增加LDH泄漏，逆转miR-29b模拟物在受损细胞中诱导的改善。综上所述，本研究结果表明，miR-29b通过负调控p53依赖性细胞凋亡途径减轻缺血性损伤，因此可能是治疗缺血性卒中的一个新的潜在治疗靶点。
Cerebral ischemic injury causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. Members of the microRNA-29 (miR-29) family are involved in regulating the process of ischemia and may be developed as biomarkers to diagnose and treat cerebral ischemia. The role of miR-29b in cerebral ischemia injury remains poorly understood. The purpose of the present study was to investigate whether miR-29b overexpression suppressed cerebral ischemic injury and to explore its underlying mechanism of action. The results demonstrated that levels of miR-29b in N2a neuroblastoma cells decreased following oxygen and glucose deprivation/reperfusion (OGD/R) treatment. Transfection with miR-29b mimics significantly increased cell viability, decreased lactate dehydrogenase (LDH) leakage, inhibited apoptosis by decreasing morphological changes occurring in the nuclei and reduced caspase-3 activity in OGD/R-treated N2a cells. Conversely, miR-29b inhibitors enhanced OGD/R-induced cytotoxicity and apoptosis. In addition, the miR-29b mimics blocked the increase in Bax and p53 expression and decreased Bcl-2 expression in OGD/R-treated N2a cells, whereas miR-29b inhibitors exacerbated the changes in the expression of these apoptosis-associated proteins caused by OGD/R. p53 knockdown using p53 small interfering RNA decreased cell viability and increased LDH leakage, reversing the improvements that the miR-29b mimics induced in damaged cells. Taken together, the results of the present study demonstrated that miR-29b attenuates ischemic injury by negatively regulating the p53-dependent apoptosis pathway and may therefore be a novel potential therapeutic target for treating ischemic stroke.
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影响因子：
10.5
作者：
Kole, Adam J.;Swahari, Vijay;Deshmukh, Mohanish
通讯作者：
Deshmukh, Mohanish
DOI：
10.1111/febs.13944
发表时间：
2016-12
期刊：
The FEBS journal
影响因子：
--
作者：
Annis RP;Swahari V;Nakamura A;Xie AX;Hammond SM;Deshmukh M
通讯作者：
Deshmukh M
影响因子：
6.3
作者：
Khanna, Savita;Rink, Cameron;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
3.9
作者：
Schuler, M;Green, DR
通讯作者：
Green, DR
影响因子：
5.3
作者：
Endo, Hidenori;Kamada, Hiroshi;Chan, Pak H.
通讯作者：
Chan, Pak H.