Chi Ma1, Yujun Pan2, Zizhen Yang3, Zhaojun Meng4, Ruohan Sun1, Tianyu Wang1, Yiping Fei1, Wenhui Fan1. 1. Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China. 2. Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China. Electronic address: panyujun2015@sina.com. 3. Department of Neurology, Qingdao Central Hospital, Qingdao, Shandong Province 266000, China. 4. Department of Ophthalmology, Fourth Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
Abstract
AIMS: In this study, we investigated the effects of Bax-inhibiting peptide (Bip)-V5, an anti-apoptosis membrane-permeable peptide, on the 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model rats. MATERIALS AND METHODS: Rats were randomly divided into five groups: Control, 6-OHDA only, Vehicle+6-OHDA, zVAD+6-OHDA, and V5+6-OHDA, that rats were preadministrated with different reagents before 6-OHDA administration. KEY FINDINGS: The result showed that intrastriatal preadministration of Bip-V5 significantly decreased the amphetamine-induced rotation of the 6-OHDA model rats and the loss of the nigral dopaminergic (DA) neurons. Moreover, Bip-V5 intrastriatal preadministration not only significantly decreased the expression of activated caspase 9 and activated caspase 3 but also decreased the enhanced expression of AIF and its nuclear translocation in the SNpc. The results in our study provide the first experimental evidence that both caspase-dependent and AIF-dependent apoptosis pathways are involved in the loss of the nigral DA neurons caused by intrastriatal administration of 6-OHDA, and intrastriatal preadministration of Bip-V5 can inhibit the above two apoptosis pathways to protect the nigral DA neurons. SIGNIFICANCE: Our results provide a new idea that Bax-inhibiting peptide may be a promising preventive or therapeutic method for PD.
AIMS: In this study, we investigated the effects of Bax-inhibiting peptide (Bip)-V5, an anti-apoptosis membrane-permeable peptide, on the 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model rats. MATERIALS AND METHODS:Rats were randomly divided into five groups: Control, 6-OHDA only, Vehicle+6-OHDA, zVAD+6-OHDA, and V5+6-OHDA, that rats were preadministrated with different reagents before 6-OHDA administration. KEY FINDINGS: The result showed that intrastriatal preadministration of Bip-V5 significantly decreased the amphetamine-induced rotation of the 6-OHDA model rats and the loss of the nigral dopaminergic (DA) neurons. Moreover, Bip-V5 intrastriatal preadministration not only significantly decreased the expression of activated caspase 9 and activated caspase 3 but also decreased the enhanced expression of AIF and its nuclear translocation in the SNpc. The results in our study provide the first experimental evidence that both caspase-dependent and AIF-dependent apoptosis pathways are involved in the loss of the nigral DA neurons caused by intrastriatal administration of 6-OHDA, and intrastriatal preadministration of Bip-V5 can inhibit the above two apoptosis pathways to protect the nigral DA neurons. SIGNIFICANCE: Our results provide a new idea that Bax-inhibiting peptide may be a promising preventive or therapeutic method for PD.
Authors: Edward J Robinson; Sebastian P Aguiar; Willemieke M Kouwenhoven; Dorinde S Starmans; Lars von Oerthel; Marten P Smidt; Lars P van der Heide Journal: Cell Death Discov Date: 2018-11-21