title: Bcl-2-associated athanogene 2 prevents the neurotoxicity of MPP+ via interaction with DJ-1.
abstract: Bcl-2-associated athanogene 2 (BAG2) is an important member in the BAG family which is characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance. The role of BAG family proteins in Parkinson's disease (PD) has not been elucidated. In this study, we demonstrated that overexpressing BAG2 ameliorates the effects of 1-methyl-4-phenylpyridinium (MPP+) in mitochondrial membrane potential (MMP) collapse, reactive oxygen species (ROS) generation, and mitochondrial release of cytochrome C. However, knockdown of DJ-1 abolished the neuroprotective effects of BAG2 against MPP+-induced neuronal toxicity. With co-immunoprecipitation and pulldown experiments, we present a direct physical interaction between BAG2 and DJ-1. Co-expression of BAG-2 together with DJ-1 increased the ratio of dimer/monomer staining intensity at the basal level. Our results indicated that MPP+ treatment leads to the disassociation of the homodimer of DJ-1. When BAG2 was overexpressed in cells, the homodimer of DJ-1 was increased. Importantly, BAG2 prevents MPP+-induced monomerization of DJ-1. Thus, our data showed that the neuroprotective effects of BAG2 are mediated by its interaction with DJ-1, strengthening the link between the BAG proteins and PD-related neurodegeneration.
authors.affiliation: Department of Neurology, Shandong Provincial Hospital, No 324 Jingwuweiqi road, Ji'nan City, Shandong Province, 250021, China.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Song
authors.forename: Shuo
authors.initials: S
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C492980:BAG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D045304:Cytochromes c; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D015655:1-Methyl-4-phenylpyridinium