敲低 TRB3 通过 MAPK 和 AKT 信号通路改善 MPP+/MPTP 诱导的帕金森病。
Knockdown of TRB3 improved the MPP/MPTP-induced Parkinson's disease through the MAPK and AKT signaling pathways.
机构信息
State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710054, China.
State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710054, China; The Biomedical-information Engineering Laboratory of State Ministry of Education Xi'an Jiaotong University, Xi'an, 710049, China.
出版信息
Neurosci Lett. 2019 Sep 14;709:134352. doi: 10.1016/j.neulet.2019.134352. Epub 2019 Jul 5.
This study aims to investigate the function and molecular mechanisms of Tribbles homolog 3 (TRB3) on the MPP/MPTP-induced Parkinson's disease (PD). In this study, MPP-induced PD cellular model and MPTP-caused PD mice model were established. Following the transfection with TRB3-shRNA, cell viability, cell apoptosis, ROS level, and the ratio of p-p38/ p38, p-JNK/JNK, p-AKT/AKT were examined. At the same time, behavior assessment of wild type female C57BL/6 mice and whole-body TRB3 knockout mice PD models caused by MPTP were performed by Rotarod test and Open-field test. The results showed that TRB3 was markedly upregulated in MPP-induced cellular model through ATF4/CHOP pathway. Knockdown of TRB3 significantly decreased the MPP-induced reduction of cell viability, augment of cell apoptosis and accumulation of ROS, inhibited the phosphorylation of p38 and JNK, and promoted the phosphorylation of AKT, in vitro. Further, knockout of TRB3 improved the behavior impairment of PD mice induced by MPTP, in vivo. In conclusion, knockdown of TRB3 has a neuroprotective effect on MPTP/MPP-induced PD cellular and mice models, through regulating MAPK and AKT signaling pathways.
本研究旨在探讨 Tribbles 同源物 3（TRB3）在 MPP/MPTP 诱导的帕金森病（PD）中的作用和分子机制。在这项研究中，建立了 MPP 诱导的 PD 细胞模型和 MPTP 诱导的 PD 小鼠模型。用 TRB3-shRNA 转染后，检测细胞活力、细胞凋亡、ROS 水平以及 p-p38/p38、p-JNK/JNK、p-AKT/AKT 的比值。同时，通过转棒试验和旷场试验对野生型雌性 C57BL/6 小鼠和全身 TRB3 敲除 PD 模型小鼠 MPTP 诱导的行为进行评估。结果表明，通过 ATF4/CHOP 通路，TRB3 在 MPP 诱导的细胞模型中明显上调。体外实验中，TRB3 的敲低显著降低了 MPP 诱导的细胞活力降低、细胞凋亡增加和 ROS 积累，抑制了 p38 和 JNK 的磷酸化，并促进了 AKT 的磷酸化。进一步，TRB3 的敲除改善了 MPTP 诱导的 PD 小鼠的行为障碍，体内实验。综上所述，敲低 TRB3 对 MPP/MPP 诱导的 PD 细胞和小鼠模型具有神经保护作用，通过调节 MAPK 和 AKT 信号通路。
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