Abstract:
:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an inducer of parkinsonism, causes degeneration of nigro-striatal dopaminergic neurons by producing its neurotoxic metabolite, 1-methyl-4-phenylpiridium ion (MPP+), by monoamine oxidase B in glial cells. We used PC12 (rat pheochromocytoma cell line) as a model cell line of dopamine-containing neurons and investigated the effects of various drugs on MPP(+)-induced cell death in PC12 cells. To estimate the cell death, we measured lactate dehydrogenase (LDH) activity leaked into the culture medium from damaged cells. When PC12 cells were treated with MPP+ at 0.3, 1.0 and 3.0 mM for 24 h, MPP+ increased the leakage of LDH and the leakage by 1.0 and 3.0 mM MPP+ was significant compared to the control. High K+ (50 mM KCl) significantly inhibited both MPP(+)-induced leakage of LDH and [3H]MPP+ uptake into the cells, suggesting that high K+ inhibits MPP(+)-induced cell death by inhibition of MPP+ uptake. NGF, dibutyryl cAMP (diBu-cAMP), cycloheximide (CHX) and aurintricarboxylic acid (ATA) significantly inhibited MPP(+)-induced leakage of LDH but did not inhibit [3H]MPP+ uptake, suggesting that these drugs inhibit MPP(+)-induced cell death at other sites than the one of MPP+ uptake.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Itano Y,Kitamura Y,Nomura Ydoi
10.1016/0197-0186(94)90017-5subject
Has Abstractpub_date
1994-11-01 00:00:00pages
419-24issue
5eissn
0197-0186issn
1872-9754journal_volume
25pub_type
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