OBJECTIVES: Parkinson's disease (PD) is the most common neurodegenerative disease in humans, and an abundance of evidence has implicated apoptosis signaling pathways in the neurodegeneration of PD. The purpose of this study was to assess the role of B-cell lymphoma 2 (Bcl-2)-associated athanogene 5 (BAG5) protein, which was previously confirmed to play an important role in the pathogenesis of PD, in the regulation of apoptosis induced by 1-methyl-4-phenyl-pyridinium (MPP(+)) in PC12 cells. METHODS: PC12 cells were treated with MPP(+) for 48 hours to induce apoptosis, and activation of Bcl-2, Bcl-xl, and caspase 3 was measured by western blot. RESULTS: The upregulation of BAG5 in PC12 cells inhibited apoptosis and increased the expression of anti-apoptotic proteins, including Bcl-2 and Bcl-xl, after MPP(+) treatment. In addition, downregulation of BAG5 in PC12 cells enhanced apoptosis and decreased the expression of these proteins after MPP(+) treatment. DISCUSSION: The data suggest that BAG5 inhibits MPP(+)-induced apoptosis through both endogenous and mitochondria-mediated pathways of apoptosis. Through this mechanism, the upregulation of BAG5 levels may occur through its anti-apoptotic activity in PD.
OBJECTIVES:Parkinson's disease (PD) is the most common neurodegenerative disease in humans, and an abundance of evidence has implicated apoptosis signaling pathways in the neurodegeneration of PD. The purpose of this study was to assess the role of B-cell lymphoma 2 (Bcl-2)-associated athanogene 5 (BAG5) protein, which was previously confirmed to play an important role in the pathogenesis of PD, in the regulation of apoptosis induced by 1-methyl-4-phenyl-pyridinium (MPP(+)) in PC12 cells. METHODS: PC12 cells were treated with MPP(+) for 48 hours to induce apoptosis, and activation of Bcl-2, Bcl-xl, and caspase 3 was measured by western blot. RESULTS: The upregulation of BAG5 in PC12 cells inhibited apoptosis and increased the expression of anti-apoptotic proteins, including Bcl-2 and Bcl-xl, after MPP(+) treatment. In addition, downregulation of BAG5 in PC12 cells enhanced apoptosis and decreased the expression of these proteins after MPP(+) treatment. DISCUSSION: The data suggest that BAG5 inhibits MPP(+)-induced apoptosis through both endogenous and mitochondria-mediated pathways of apoptosis. Through this mechanism, the upregulation of BAG5 levels may occur through its anti-apoptotic activity in PD.
Authors: Manish K Gupta; Farzaneh G Tahrir; Tijana Knezevic; Martyn K White; Jennifer Gordon; Joseph Y Cheung; Kamel Khalili; Arthur M Feldman Journal: J Cell Biochem Date: 2016-01-21 Impact factor: 4.429
Authors: Mitchell L De Snoo; Erik L Friesen; Yu Tong Zhang; Rebecca Earnshaw; Geneviève Dorval; Minesh Kapadia; Darren M O'Hara; Victoria Agapova; Hien Chau; Ornella Pellerito; Matthew Y Tang; Xinzhu Wang; Gerold Schmitt-Ulms; Thomas M Durcan; Edward A Fon; Lorraine V Kalia; Suneil K Kalia Journal: Cell Death Dis Date: 2019-12-02 Impact factor: 8.469