Increase of antioxidative potential by tert-butylhydroquinone protects against cell death associated with 6-hydroxydopamine-induced oxidative stress in neuroblastoma SH-SY5Y cells.

Abstract

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.

• Authors: Hirokazu Hara, Mitsuhiro Ohta, Kiyoe Ohta, Sadako Kuno, Tetsuo Adachi
• Journal: Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 119 Issue 2 Pg. 125-31 (Nov 26 2003) ISSN: 0169-328X [Print] Netherlands
• PMID: 14625079 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Hydroquinones
• Neuroprotective Agents
• RNA, Messenger
• Reactive Oxygen Species
• Oxidopamine
• 2-tert-butylhydroquinone
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• Glutathione

Topics

• Antioxidants (pharmacology)
• Cell Death (drug effects, physiology)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Glutathione (metabolism)
• Humans
• Hydroquinones (pharmacology)
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases (metabolism)
• Models, Neurological
• NAD(P)H Dehydrogenase (Quinone) (genetics)
• Neuroblastoma
• Neurons (drug effects, enzymology, pathology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects, physiology)
• Oxidopamine
• Parkinson Disease (drug therapy, enzymology)
• RNA, Messenger (drug effects, metabolism)
• Reactive Oxygen Species (metabolism)
• Transcriptional Activation (drug effects, physiology)