Involvement of endoplasmic reticulum stress on the cell death induced by 6-hydroxydopamine in human neuroblastoma SH-SY5Y cells.
Endoplasmic reticulum (ER) dysfunction is known to activate the unfolded protein response, which is characterized by the activation of two divergent processes, i.e., suppression of the initiation process in global protein synthesis and expression of glucose-regulated protein 78 (Bip/Grp78) and the C/EBP homologous transcription factor CHOP/Gadd153. In this study, we examined the expression of CHOP/Gadd153 and Bip/Grp78 in human neuroblastoma SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA), which is used to prepare animal models of Parkinson's disease. 6-OHDA treatment induced cell death, in a concentration-dependent manner, which was inhibited by co-treatment with an antioxidant N-acetylcysteine. 6-OHDA was also effective in decreasing proteasome activity and in increasing the levels of high molecular ubiquitin-conjugated proteins. Furthermore, 6-OHDA induced a marked increase in the expression of both CHOP/Gadd153 and Bip/Grp78. This increase was prevented by N-acetylcysteine. Taken together, our data indicate that ER dysfunction is at least in part involved in the mechanisms underlying cell death induced by 6-OHDA in SH-SY5Y cells.
Yamamuro
Akiko
A
Faculty of Pharmaceutical Sciences, Departments of Pharmacotherapeutics, Setsunan University, 45-1 Nagaotoge-cho, 573-0101 Hirakata, Osaka, Japan. yamamuro@pharm.setsunan.ac.jp
Yoshioka
Yasuhiro
Y
Ogita
Kiyokazu
K
Maeda
Sadaaki
S
D000111:Acetylcysteine / Q000378:metabolism; D051702:Activating Transcription Factor 6 / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D016166:Free Radical Scavengers / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009447:Neuroblastoma; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D018663:Adrenergic Agents; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D016166:Free Radical Scavengers; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D016627:Oxidopamine; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine