Cytotoxic effects of MPTP on SH-SY5Y human neuroblastoma cells.
Morphological and metabolic endpoints were used to evaluate MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity to SH-SY5Y human neuroblastoma cells. After 8 hours of exposure, MPTP was found to affect cell viability only at a very high concentration (3 x 10(-3) M), but its metabolite MPP+ could decrease viability at 10(-4) M. MPTP, via its metabolite MPP+, inhibited NADH dehydrogenase activity when concentrations exceeded 10(-4) M (for MPP+ 10(-5)M). The Ki were 2.4 x 10(-3) M and 3 x 10(-4)M for MPTP and MPP+, respectively. MPTP at concentrations greater than 10(-4) M altered cell morphology as early as one hour after exposure. These changes included formation of cell surface blebs and attenuated neurites. After 8 hours at 10(-3) M and 24 hrs at 10(-4) M, MPTP caused ultrastructural changes of mitochondria with increased electron-density of the matrix and disorganization of cristae, as well as abnormal aggregation of filamentous material of the cytoskeleton. Because these changes of structure and function took place at concentrations lower than those needed to affect cell viability, they may play a role in MPTP neurotoxicity in SH-SY5Y cell culture.
Song
X
X
Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061-0442, USA.
Perkins
S
S
Jortner
B S
BS
Ehrich
M
M
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D001932:Brain Neoplasms / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D015259:Dopamine Agents / Q000633:toxicity*; D006801:Humans; D020267:MPTP Poisoning; D009245:NADH Dehydrogenase / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D014407:Tumor Cells, Cultured
D015259:Dopamine Agents; D009245:NADH Dehydrogenase; D015655:1-Methyl-4-phenylpyridinium