Abstract
Loss-of-function mutations in gene encoding DJ-1 contribute to the pathogenesis of autosomal recessive early-onset familial forms of Parkinson's disease (PD). DJ-1 is a multifunctional protein and plays a protective role against oxidative stress-induced mitochondrial damage and cell death, but the exact mechanism underlying this is not yet clearly understood. Here, using coimmunoprecipitation (Co-IP) and immunofluorescence methods, we prove that Bcl-2-associated athanogene 5 (BAG5), a BAG family member, interacts with DJ-1 in mammalian cells. Moreover, we show that BAG5 could decrease stability of DJ-1 and weaken its role in mitochondrial protection probably by influencing dimerization in stress condition. Our study reveals the relationship of BAG5 and DJ-1 suggesting a potential role for BAG5 in the pathogenesis of PD through its functional interactions with DJ-1.
MeSH terms
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Adaptor Proteins, Signal Transducing / antagonists & inhibitors
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Apoptosis / drug effects
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HEK293 Cells
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HSP70 Heat-Shock Proteins / antagonists & inhibitors
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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Humans
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Immunoprecipitation
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Membrane Potential, Mitochondrial / drug effects
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Microscopy, Fluorescence
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Mitochondria / metabolism*
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Neuroprotective Agents / metabolism*
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Oxidative Stress*
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Protein Deglycase DJ-1 / genetics
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Protein Deglycase DJ-1 / metabolism*
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RNA Interference
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RNA, Small Interfering / metabolism
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Reactive Oxygen Species / metabolism
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Rotenone / pharmacology
Substances
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Adaptor Proteins, Signal Transducing
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BAG5 protein, human
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HSP70 Heat-Shock Proteins
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Neuroprotective Agents
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RNA, Small Interfering
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Reactive Oxygen Species
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Rotenone
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Protein Deglycase DJ-1