title: MPTP-induced reactive oxygen species promote cell death through a gradual activation of caspase-3 without expression of GRP78/Bip as a preventive measure against ER stress in PC12 cells.
abstract: Glucose-regulated protein 78 (GRP78)/Immunoglobulin binding protein (Bip) is a chaperone which functions to protect cells from endoplasmic reticulum (ER) stress. GRP78/Bip is expressed following ER stress induced by thapsigargin, tunicamycin or chemical factors. However, the mechanism of progression of ER stress against stress factors is still obscure. We examined whether reactive oxygen species (ROS) were involved in GRP78/Bip expression and caspase-3 activity was induced in PC12 cells using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce ROS. We report that PC12 cells lost viability in the presence of MPTP for 24 hours as a partial effect of ROS. We also show that N-acetyl-L-cysteine diminished the MPTP-induced apoptosis with expunction of ROS. Furthermore, we observed that GRP78/Bip was not up-regulated and the caspase-3 activity was increased in the presence of MPTP. These results suggest that insubstantial ROS do not contribute to the ER stress-mediated cell death while caspase-3 is involved in ROS-promoted cell death in MPTP-treated cells.
authors.affiliation: Laboratory of Neurobiology, Faculty of Engineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan. shimoke@ipcku.kansai-u.ac/jp
authors.forename: Koji
authors.initials: K
authors.lastname: Shimoke
authors.forename: Motoshige
authors.initials: M
authors.lastname: Kudo
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeuchi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation / Q000187:drug effects; D006360:Heat-Shock Proteins; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000032:analysis; D018832:Molecular Chaperones / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008054:Lipid Peroxides; D018832:Molecular Chaperones; D017382:Reactive Oxygen Species; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases