Pramipexole attenuates neuronal injury in Parkinson's disease by targeting miR-96 to activate BNIP3-mediated mitophagy. (June 2021)

• Record Type: Journal Article
• Authors: Wang, Dong-Xin; Yang, Ying; Huang, Xiao-Song; Tang, Jia-Yu; Zhang, Xi; Huang, Hong-Xing; Zhou, Bin; Liu, Bo; Xiao, Hui-Qiong; Li, Xiao-Hui; Yang, Ping; Zou, Shu-Cheng; Liu, Kun; Wang, Xiao-Ye; Li, Xiao-Song
• Is Part Of: Neurochemistry international. Volume 146(2021)
• Publication Date: 2021-06
• Subjects: Parkinson's disease -- Pramipexole -- miR-96 -- BNIP3 -- Mitophagy; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2021.104972
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: 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. Highlights: PPX weakens MPP + -caused neuronal injury and apoptosis. PPX suppresses miR-96 and activates BNIP3-mediated mitophagy. miR-96 weakens the influence of PPX on MPP + -caused neuronal damage. miR-96 targets BNIP3 to inhibit PINK1/Parkin signals-mediated mitophagy. PPX mitigates MPTP-induced neuronal injury in mice by miR-96/BNIP3 axis.