|
KMID : 0360419950310020165
|
|
Korean Journal of Pharmacology
1995 Volume.31 No. 2 p.165 ~ p.177
|
|
|
Studies on the Depaminergic Neuronal Toxicity of MPTP and its Pyridium Metabolite, MPP^(+)
|
|
|
|
|
Abstract
|
|
|
Dissociated cell cultures from rat embryonic ventral mesencephalon were used to evaluate the mechanisms of MPP- neurotoxicity. The cells were treated with MPTP or MPP` and the viability of the cells was assessed biochemically; tyrosine hydroxylase (TH) immunoreactivity, protem, intracellular ATP and lactate content and lipid peroxidation. Also the generation of the intracellular oxidants was measured after loading 2´, 7´-dichlorofluorescin diacetate to the cells.
When cultures were exposed to 0.1 mM MPP+, at 2 hour incubation lactate was significantly accumulated in the cells and then the intracellul&r ATP content and TH immunoreactivity, were decreased dose- and time-dependently. But, malondialdehyde as an index for lipid peroxidation was not changed even though the-generation of the intracellular oxidants was stimulated by the addition of MPP^+
On the other hand, 1 mM MPTP significantly reduced the TH immunoreactivity at 24 hour exposure without any change in the intracellular ATP, lactate and MDA content until 6 hour exposure. And also MPTP inhibited the generation of the intracellular oxidants from control cells and MPP^+ exposed cells.
These results indicate that cytotoxicity of MPP^+ is mediated by inhibiting the mitochondrial energy metabolism rather than generating the intracellular oxidants. And MPTP would have direct action in addition to conveting to the toxic metabolite, MPP^- to exert the toxicity on the dopaminergic neurons.
|
|
|
KEYWORD
|
|
|
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
|
|