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Differences in the disposition and toxicity of 1-methyl-4-phenylpyridinium in cultured rat and mouse astrocytes

✍ Scribed by May J. Tsai; Dr. Eminy H. Y. Lee

Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
735 KB
Volume
12
Category
Article
ISSN
0894-1491

No coin nor oath required. For personal study only.

✦ Synopsis

Species difference in the susceptibility to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) was investigated in cultured rat and mouse astrocytes, where 1-methyl-4-phenylpyridinium (MPP+), the toxic mediator of MPTP, is formed. Type A monoamine oxidase (MAO) predominated in both rat and mouse astrocytes, while its activity was slightly higher in mouse cells compared to rat cells; MAO-B activity, on the other hand, was significantly lower in mouse astrocytes than in rat astrocytes. Because both types of MA0 have been reported to make similar contributions to MPP' production in astrocytes, their total activity was examined and results indicated that there was no significant difference between these two species. In addition, MPP' caused a dosedependent loss of cell viability as judged by the amount of lactate dehydrogenase released into the incubation medium. The toxicity of MPP+ on astrocytes started to be seen after a 2 day incubation period. Mouse astrocytes were more vulnerable to MPP' than rat astrocytes. The threshold values for MPP+ toxicity in mouse and rat cultures were 10 pM and 70 pM, respectively. After addition of [3H] MPP+ to the medium, intracellular ["HI MPP' was found to increase in both cultures. Mouse astrocytes accumulated more MPP+ than rat astrocytes (150 pmoVmg protein vs. 65 pmoVmg protein). When astrocytes were allowed to accumulate [3H] MPP' and then incubated in fresh medium not containing [3H] MPP', intracellular levels of [3H] MPP+ in both cells rapidly declined (110 pmol/ protein in mouse vs. 40 pmoVmg protein in rat of MPP+ been released). These results indicated that 1) MPP+ could cross the plasma membrane of astrocytes despite of its charged chemical structure, 2) mouse astrocytes had a higher capacity for MPP' accumulation (approximately 2-fold1, as well as release (approximately 2.7-fold), than rat astrocytes, and 3) mouse astrocytes were more vulnerable to MPP+ than rat astrocytes.

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