普拉克索通过靶向 miR-96 激活 BNIP3 介导的线粒体自噬来减轻帕金森病中的神经元损伤。
Pramipexole attenuates neuronal injury in Parkinson's disease by targeting miR-96 to activate BNIP3-mediated mitophagy.
机构信息
The Research Institute of Mentality and Sanitation, Hunan Provincial Brain Hospital, Changsha, 410007, Hunan Province, PR China.
Medical Department of Neurology, Hunan Provincial Brain Hospital, Changsha, 410007, Hunan Province, PR China.
出版信息
Neurochem Int. 2021 Jun;146:104972. doi: 10.1016/j.neuint.2021.104972. Epub 2021 Jan 22.
BACKGROUND
Parkinson's disease is a common neurodegenerative problem. Pramipexole (PPX) plays protective role in Parkinson's disease. Nevertheless, the mechanism of PPX in Parkinson's disease-like neuronal injury is largely uncertain.
METHODS
1-methyl-4-phenylpyridinium (MPP)-stimulated neuronal cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice were used as the model of Parkinson's disease. MPP-induced neuronal injury was assessed via cell viability, lactic dehydrogenase (LDH) release and apoptosis. microRNA-96 (miR-96) and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) abundances were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blotting. Mitophagy was tested by Western blotting and immunofluorescence staining. MPTP-induced neuronal injury in mice was investigated via behavioral tests and TUNEL.
RESULTS
PPX alleviated MPP-induced neuronal injury via increasing cell viability and decreasing LDH release and apoptosis. PPX reversed MPP-induced miR-96 expression and inhibition of mitophagy. miR-96 overexpression or BNIP3 interference weakened the suppressive role of PPX in MPP-induced neuronal injury. miR-96 targeted BNIP3 to inhibit PTEN-induced putative kinase 1 (PINK1)/Parkin signals-mediated mitophagy. miR-96 overexpression promoted MPP-induced neuronal injury via decreasing BNIP3. PPX weakened MPTP-induced neuronal injury in mice via regulating miR-96/BNIP3-mediated mitophagy.
CONCLUSION
PPX mitigated neuronal injury in MPP-induced cells and MPTP-induced mice by activating BNIP3-mediated mitophagy via directly decreasing miR-96.
背景
帕金森病是一种常见的神经退行性疾病。普拉克索（PPX）在帕金森病中发挥保护作用。然而，PPX 在帕金森病样神经元损伤中的作用机制在很大程度上尚不清楚。
方法
使用 1-甲基-4-苯基吡啶鎓（MPP）刺激的神经元细胞和 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠作为帕金森病模型。通过细胞活力、乳酸脱氢酶（LDH）释放和细胞凋亡来评估 MPP 诱导的神经元损伤。通过定量逆转录聚合酶链反应（qRT-PCR）或 Western blot 检测 microRNA-96（miR-96）和 BCL2/腺病毒 E1B 19kDa 相互作用蛋白 3（BNIP3）的丰度。通过 Western blot 和免疫荧光染色检测自噬。通过行为测试和 TUNEL 研究 MPTP 诱导的小鼠神经元损伤。
结果
PPX 通过增加细胞活力、降低 LDH 释放和凋亡来减轻 MPP 诱导的神经元损伤。PPX 逆转了 MPP 诱导的 miR-96 表达和自噬抑制。miR-96 过表达或 BNIP3 干扰减弱了 PPX 对 MPP 诱导的神经元损伤的抑制作用。miR-96 靶向 BNIP3 抑制 PTEN 诱导的假定激酶 1（PINK1）/Parkin 信号介导的自噬。miR-96 过表达通过降低 BNIP3 促进 MPP 诱导的神经元损伤。PPX 通过调节 miR-96/BNIP3 介导的自噬减弱了 MPTP 诱导的小鼠神经元损伤。
结论
PPX 通过直接降低 miR-96 激活 BNIP3 介导的自噬来减轻 MPP 诱导的细胞和 MPTP 诱导的小鼠神经元损伤。
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