Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells

We examined the inhibitory effect of tetrahydrobiopterin (BPH4) on L-β-(3,4-dihydroxyphenyl)alanine (DOPA)-induced cytotoxicity in PC-12 cells. First in vitro inhibitory efficacy of BPH4 on lipid peroxidation induced by Fe3+-DOPA complex was confirmed by using PC-liposomes. Fe3+-DOPA complex at 50 μ...

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Main Authors: Kojima Shuji, Kugenuma Hiroshi, Oyobe Sayaka, lizuka Hiroyuki, Ikekita Masahiko
Format: Article
Language:English
Published: De Gruyter 1997-01-01
Series:Pteridines
Subjects:
Online Access:https://doi.org/10.1515/pteridines.1997.8.1.10
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author Kojima Shuji
Kugenuma Hiroshi
Oyobe Sayaka
lizuka Hiroyuki
Ikekita Masahiko
author_facet Kojima Shuji
Kugenuma Hiroshi
Oyobe Sayaka
lizuka Hiroyuki
Ikekita Masahiko
author_sort Kojima Shuji
collection DOAJ
description We examined the inhibitory effect of tetrahydrobiopterin (BPH4) on L-β-(3,4-dihydroxyphenyl)alanine (DOPA)-induced cytotoxicity in PC-12 cells. First in vitro inhibitory efficacy of BPH4 on lipid peroxidation induced by Fe3+-DOPA complex was confirmed by using PC-liposomes. Fe3+-DOPA complex at 50 μM caused drastic lipid peroxidation, which was significantly inhibited by BPH4 in a dose-dependent manner. Next, we confirmed the in vitro potency of BPH4 in cultured PC-12 cells. Fe3+-DOPA complex exerted time-and dose-dependent cytotoxicity, which was also dose-dependently inhibited by BPH4 possessed almost the same potency as deferoxamine and α-tocopherol. We also examined the cytotoxicity of DOPA itself. A higher dose of DOPA (250 μM) was necessary to afford the same cytotoxic potency towards PC-12 cells as that of Fe3+-DOPA complex (50 μM). The toxicity was essentially abolished by SOD and BPH4 and ameliorated by catalase . However, deferoxamine did not modify the toxicity. In conclusion, BPH4 protects both PC-liposomes and PC-12 cells from damage induced by DOPA with and without ferric ion, and may inhibit the degeneration of dopamine neurons through its antioxidatiye activity.
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spelling doaj.art-1584b18517a34bc8b9139c9141fd2b1f2022-12-21T21:34:46ZengDe GruyterPteridines0933-48072195-47201997-01-0181101610.1515/pteridines.1997.8.1.10Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 CellsKojima Shuji0Kugenuma Hiroshi1Oyobe Sayaka2lizuka Hiroyuki3Ikekita Masahiko4Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, JapanResearch Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, JapanResearch Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, JapanResearch Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, JapanResearch Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, JapanWe examined the inhibitory effect of tetrahydrobiopterin (BPH4) on L-β-(3,4-dihydroxyphenyl)alanine (DOPA)-induced cytotoxicity in PC-12 cells. First in vitro inhibitory efficacy of BPH4 on lipid peroxidation induced by Fe3+-DOPA complex was confirmed by using PC-liposomes. Fe3+-DOPA complex at 50 μM caused drastic lipid peroxidation, which was significantly inhibited by BPH4 in a dose-dependent manner. Next, we confirmed the in vitro potency of BPH4 in cultured PC-12 cells. Fe3+-DOPA complex exerted time-and dose-dependent cytotoxicity, which was also dose-dependently inhibited by BPH4 possessed almost the same potency as deferoxamine and α-tocopherol. We also examined the cytotoxicity of DOPA itself. A higher dose of DOPA (250 μM) was necessary to afford the same cytotoxic potency towards PC-12 cells as that of Fe3+-DOPA complex (50 μM). The toxicity was essentially abolished by SOD and BPH4 and ameliorated by catalase . However, deferoxamine did not modify the toxicity. In conclusion, BPH4 protects both PC-liposomes and PC-12 cells from damage induced by DOPA with and without ferric ion, and may inhibit the degeneration of dopamine neurons through its antioxidatiye activity.https://doi.org/10.1515/pteridines.1997.8.1.10tetrahydrobiopterindopacytotoxicitypc-12 cells
spellingShingle Kojima Shuji
Kugenuma Hiroshi
Oyobe Sayaka
lizuka Hiroyuki
Ikekita Masahiko
Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells
Pteridines
tetrahydrobiopterin
dopa
cytotoxicity
pc-12 cells
title Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells
title_full Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells
title_fullStr Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells
title_full_unstemmed Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells
title_short Suppressive Effect of Tetrahydrobiopterin on L-β-( 3,4-Dihydroxyphenyl) alanine-Induced Cytotoxicity in PC-12 Cells
title_sort suppressive effect of tetrahydrobiopterin on l β 3 4 dihydroxyphenyl alanine induced cytotoxicity in pc 12 cells
topic tetrahydrobiopterin
dopa
cytotoxicity
pc-12 cells
url https://doi.org/10.1515/pteridines.1997.8.1.10
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