title: Pre-administration of BAX-inhibiting peptides decrease the loss of the nigral dopaminergic neurons in rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our results provide a new idea that Bax-inhibiting peptide may be a promising preventive or therapeutic method for PD.
authors.affiliation: Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China. Electronic address: panyujun2015@sina.com.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Neurology, Qingdao Central Hospital, Qingdao, Shandong Province 266000, China.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Fourth Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
authors.forename: Ruohan
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fei
authors.affiliation: Department of Neurology, First Hospital and Clinical College of Harbin Medical University, Harbin, Heilongjiang Province 150001, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Fan
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis / Q000235:genetics; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D053453:Caspase 9 / Q000096:biosynthesis / Q000235:genetics; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects*; D006892:Hydroxydopamines; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; C494828:Bax protein, rat; D018765:Dopamine Uptake Inhibitors; D006892:Hydroxydopamines; D018696:Neuroprotective Agents; D009842:Oligopeptides; C509183:Val-Pro-Met-Leu-Lys; D051028:bcl-2-Associated X Protein; D000661:Amphetamine; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9
keywords: 6-Hydroxydopamine; Apoptosis; Bax-inhibiting peptide; Dopaminergic neurons; Parkinson's disease