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Cytotoxic effects of MPTP on SH-SY5Y human neuroblastoma cells
X Song1, S Perkins, B S Jortner
1Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061-0442, USA.
Abstract:
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.
Insights
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+ cause neurotoxic effects in human neuroblastoma cells. These toxins alter cell morphology and mitochondrial function at lower concentrations than those affecting cell viability.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin implicated in Parkinson's disease.
- SH-SY5Y human neuroblastoma cells are a common model for studying neuronal toxicity.
Purpose of the Study:
- To evaluate the toxic effects of MPTP and its metabolite MPP+ on SH-SY5Y cells.
- To investigate the morphological and metabolic changes induced by MPTP and MPP+.
Main Methods:
- Exposure of SH-SY5Y cells to varying concentrations of MPTP and MPP+.
- Assessment of cell viability, NADH dehydrogenase activity, and cell morphology.
- Ultrastructural analysis of mitochondria and cytoskeleton.
Main Results:
- MPP+ decreased cell viability at 10(-4) M, while MPTP required higher concentrations (3 x 10(-3) M).
- MPTP and MPP+ inhibited NADH dehydrogenase activity at concentrations above 10(-4) M.
- MPTP altered cell morphology (blebs, attenuated neurites) and induced mitochondrial/cytoskeletal damage at lower concentrations than those affecting viability.
Conclusions:
- MPTP-induced neurotoxicity in SH-SY5Y cells involves early morphological and mitochondrial alterations.
- These structural and functional changes precede significant loss of cell viability and may contribute to MPTP's neurotoxic mechanism.