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  • 1
    ISSN: 1435-1463
    Keywords: Keywords: Cytotoxicity ; catechol isoquinolines ; endogenous neurotoxin ; hydroxyl radical ; oxidative phosphorylation ; SH-SY5Y cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The mechanism of the cytotoxicity of endogenous dopaminederived (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-N-methylsalsolinol] to differentiated human dopaminergic neuroblastoma SH-SY5Y cells was studied using a reduction-oxidation indicator, Alamar Blue. N-Methylsalsolinol and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, were found to inhibit oxidative phosphorylation, as shown by the Redox capacity. Antioxidants, such as reduced glutathione, catalase, Tris and n-propyl gallate, reduced the cytotoxicity of N-methylsalsolinol, suggesting that hydroxyl radical was the major reactive oxygen species for the cytotoxicity. Deprenyl also protected the cells from the decrease of the Redox capavity by N-methylsalsolinol. However, antioxidants did not protect the cells from the cytotoxicity of the catechol isoquinolinium ion. The results suggest that oxidative stress induced by hydroxyl radical may be involved in the cell death of dopaminergic neurons by N-methylsalsolinol.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Uptake ; inhibition ; dopamine transporter ; 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline ; 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline ; 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion ; neuroblastoma SH-SY5Y cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Uptake of catechol isoquinolines to dopamine cells was studied using human dopaminergic neuroblastoma SH-SY5Y cells. Only (R)-1,2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-1,2-DiMeDHTIQ] was transported by dopamine uptake system, while (S)-1,2-DiMeDHTIQ, (R)- and (S)-1-methyl-6,7-dihydroxy-tetrahydroisoquinoline, and 1,2-dimethyl-6,7-dihydroxyisoquinolinum ion were not. Kinetical study showed that the uptake of (R)-1,2-DiMeDHTIQ followed the Michaelis-Menten equation, and the values of the Michaelis constant and the maximal velocity were obtained to be 102.6 ± 36.9 μM and 66.0 ± 2.8 pmol/min/mg protein. Dopamine was found to inhibit (R-1-DiMeDHTIQ uptake competitively. These results suggest that the selective uptake by dopamine transporter may account for the specific neurotoxicity of (R)-1,2-DiMeDHTIQ to dopamine neurons.
    Type of Medium: Electronic Resource
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