1-Methyl-4-phenylpyridinium (MPP+)-induced cell death in PC12 cells: inhibitory effects of several drugs.

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 Int

authors

Itano Y,Kitamura Y,Nomura Y

doi

10.1016/0197-0186(94)90017-5

subject

Has Abstract

pub_date

1994-11-01 00:00:00

pages

419-24

issue

5

eissn

0197-0186

issn

1872-9754

journal_volume

25

pub_type

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