Increase of antioxidative potential by tert-butylhydroquinone protects against cell death associated with 6-hydroxydopamine-induced oxidative stress in neuroblastoma SH-SY5Y cells.
Recent findings suggest that oxidative stress caused by dopamine could be closely involved in the pathogenesis of Parkinson's disease (PD). tert-Butylhydroquinone (tBHQ) is known as a strong inducer of phase II detoxification enzymes which have antioxidative functions. In this study, we investigated the neuroprotective effect of tBHQ against 6-hydroxydopamine (6-OHDA)-induced cell death using human neuroblastoma SH-SY5Y cells. The pretreatment of SH-SY5Y cells with tBHQ significantly reduced 6-OHDA-induced generation of reactive oxygen species (ROS), the phosphorylation of c-Jun N-terminal kinase (JNK), and subsequent cell death. We also observed that tBHQ increased the intracellular glutathione levels and induced the expression of NAD(P)H:quinone oxidoreductase (NQO1) mRNA. In addition, tBHQ dose-dependently activated the antioxidant responsive element (ARE), which plays a key role in the transcriptional activation of phase II detoxification enzymes including NQO1. These results indicate that an increase of intracellular antioxidative potential in SH-SY5Y cells by tBHQ treatment protects cells from 6-OHDA-induced oxidative stress.
Hara
Hirokazu
H
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Ohta
Mitsuhiro
M
Ohta
Kiyoe
K
Kuno
Sadako
S
Adachi
Tetsuo
T
D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008959:Models, Neurological; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D006873:Hydroquinones; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016627:Oxidopamine; C018855:2-tert-butylhydroquinone; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione