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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Format: | Article |
Language: | English |
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De Gruyter
1997-01-01
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Series: | Pteridines |
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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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institution | Directory Open Access Journal |
issn | 0933-4807 2195-4720 |
language | English |
last_indexed | 2024-12-17T19:48:54Z |
publishDate | 1997-01-01 |
publisher | De Gruyter |
record_format | Article |
series | Pteridines |
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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