CYTOTOXIC EFFECTS OF MPTP ON SH-SY5Y HUMAN NEUROBLASTOMA-CELLS

Morphological and metabolic endpoints were used to evaluate MPTP (1-me thyl-4-phenyl-1,2,3,6-tetrahydropyridine) toxicity to SH-SY5Y, human n euroblastoma cells. After 8 hours of exposure, MPTP was found to affec t cell viability only at a very high concentration (3x10(-3) M) but it s metabolite MPP+ could decrease viability at 10(-4) M. MPTP, via its metabolite MPP+, inhibited NADH dehydrogenase activity when concentrat ions exceeded 10(-4) M (for MPP+ 10(-5) M). The K-j, were 2.4 x 10(-3) M and 3 x 10(-4) M for MPTP and MPP, respectively. MPTP at concentrat ions greater than 10(-4) M altered cell morphology as early as one hou r after exposure. These changes included formation of cell surface ble bs and attenuated neurites. After 8 hours at 10(-3) M and 24 hrs at 10 (-4) M, MPTP caused ultrastructural changes of mitochondria with incre ased electron-density of the matrix and disorganization of cristae, as well as abnormal aggregation of filamentous material of the cytoskele ton. changes of stucture and function took place at concentrations low er than those needed to affect cell viability, they may play a role in MPTP neurotoxicity in SH-SY5Y cell culture. (C) 1997 Inter Press, Inc .