Detection of a novel neurotoxic metabolite of Parkinson’s disease-related neurotoxin, 1-benzyl-1,2,3,4- tetrahydroisoquinoline
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- Kotake Yaichiro
- Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Sekiya Yoko
- Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Okuda Katsuhiro
- Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Ohta Shigeru
- Graduate School of Biomedical and Health Sciences, Hiroshima University
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抄録
Naturally occurring low-molecular weight compounds with a chemical structure like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline(1BnTIQ), are candidates for the endogenous neurotoxins that cause Parkinson’s disease (PD). 1BnTIQ is an endogenous amine in human CSF and increases in the CSF of patients with PD. It inhibits complex Iand elicits PD-like behavioral abnormalities in monkey and mouse. In this study, we searched metabolites of 1BnTIQ by rat liver S9 using liquid chromatography-tandem mass spectrometry, and identified a dehydrated metabolite, 1-benzyl-3,4-dihydroisoquinoline (1BnDIQ). 1BnDIQ was identified by corresponding mass spectra and precursor ion scans in authentic and complete enzyme samples. Multiple reaction monitoring analysis showed microsome-dependent 1BnDIQ production. We previously reported that 1BnDIQ is more toxic than 1BnTIQ in cytotoxicity study in SH-SY5Y neuroblastoma cells. In addition, 1BnTIQ is reported to pass through the blood-brain barrier of the rat brain, and 1BnDIQ is supposed to be more lipophilic than 1BnTIQ. 1BnDIQ may easily reach the brain, and it might contribute to PD-related neurotoxicity.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 39 (5), 749-754, 2014
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204905796224
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- NII論文ID
- 130004690962
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- NII書誌ID
- AN00002808
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- COI
- 1:STN:280:DC%2BC2M7jsFOhsQ%3D%3D
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 025850981
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- PubMed
- 25242405
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
- CiNii Articles
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