Marongiu M E, Piccardi M P, Bernardi F, Corsini G U, Del Zompo M
Institute of Microbiology, University of Cagliari, Italy.
Neurosci Lett. 1988 Dec 5;94(3):349-54. doi: 10.1016/0304-3940(88)90043-2.
This study was designed to investigate the toxicity of both MPTP and MPP+ using some simple cell systems, such as PC12 and C6 cultures, as models. Exposure of PC12 cells to 0.5 mM MPTP for 72 h resulted in a 50% cell loss with respect to the control cells, and clorgyline, a MAO-A inhibitor, antagonized this toxic effect. Higher concentrations of MPTP demonstrated only a weak cytostatic effect on C6 cells. Moreover, MPP+ showed a toxic effect which was 100 times more evident than MPTP toxicity in the PC12. We found a single, saturable class of [3H]MPP+ binding sites with a relatively high affinity both in PC12 and C6 cell lines. Moreover, the most susceptible cell line towards the toxic effects of both MPTP and MPP+, i.e. PC12, has the higher number of MPP+ binding sites. Our results suggest that MPTP can be toxic not only via MAO-B, but also via MAO-A activity and we propose PC12 as a model to study the intracellular mechanisms of MPTP and MPP+ toxicity.
本研究旨在使用一些简单的细胞系统，如PC12和C6培养物作为模型，来研究MPTP和MPP⁺的毒性。将PC12细胞暴露于0.5 mM MPTP中72小时，相对于对照细胞导致50%的细胞损失，而MAO-A抑制剂氯吉兰可拮抗这种毒性作用。更高浓度的MPTP对C6细胞仅表现出微弱的细胞生长抑制作用。此外，MPP⁺在PC12中显示出比MPTP毒性明显100倍的毒性作用。我们在PC12和C6细胞系中发现了一类单一的、可饱和的[³H]MPP⁺结合位点，其具有相对较高的亲和力。此外，对MPTP和MPP⁺的毒性作用最敏感的细胞系，即PC12，具有更多的MPP⁺结合位点。我们的结果表明，MPTP不仅可通过MAO-B产生毒性，还可通过MAO-A活性产生毒性，并且我们提出将PC12作为研究MPTP和MPP⁺毒性细胞内机制的模型。
