Uptake and metabolism of MPTP and MPP+ in SH-SY5Y human neuroblastoma cells

The human neuroblastoma cell line, SH-SY5Y, has the potential to be used as an in vitro model for the Study of the neurotoxicity of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). The ability of SH-SY5Y cells to metabolize MPTP and. to take up 1-methyl-4-phenylpyridinium (MPP+) and dopamine (DA) were, therefore, investigated. The results indicated that SH-SY5Y cells take up MPP+ specifically through a DA uptake mechanism, whereas MPTP enters cells through a non-DA transport mechanism. The K-d values for DA and MPP+ were 116.54 and 18.65 nM, respectively. The V-max for DA and MPP+ were 42.43 and 54.88 fmol/min/mg protein, respectively. SH-SY5Y cells were also capable of metabolizing MPTP to MPDP+ and MPP+ using the same enzyme (MAO-B) that is used in vivo. Neurotoxicity of MPTP in animals and in man occurs after conversion to MPP+ and uptake into susceptible cells by the DA transport system. Because SH-SY5Y cells can both metabolize MPTP and take up MPP+, this cell line may be more suitable than those that lack a DA uptake system or MAO-E as an in vitro system for studies on uptake and metabolism associated with the neurotoxicity of MPTP and its analogues.