MPP+ induced apoptotic cell death in SH-SY5Y neuroblastoma cells: an electron microscope study.
PD is a common, late-onset neurodegenerative disorder that results in part from the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The neurotoxin MPTP can induce PD-like clinical symptomatology and neuropathological destruction and, thus, has been used as a PD model. The human neuroblastoma cell line SH-SY5Y possesses many of the qualities of human neurons and, as such, has served as a model for them. Apoptosis is the mode of cell death induced in SH-SY5Y cells by MPTP, and this was confirmed with nick end labeling and bisbenzimide staining. Transmission electron microscopic analysis of the ultrastructural changes occurring in neurotoxin exposed SH-SY5Ys revealed many morphological characteristics consistent with apoptosis. These changes included plasmalemmal blebbing, altered cytosolic density, nuclear condensation and fragmentation, pronounced vacuole formation, ribosomal dispersion, and the disappearance of the golgi complex, microtubules, and smooth endoplasmic reticulum. Limited amounts of rough endoplasmic reticulum and mitochondria exhibited normal morphology throughout the apoptotic changes but then were disrupted during secondary necrotic changes. The in vitro induction of apoptosis by a parkinsonism neurotoxin might be reflective of the mechanisms of in vivo nigral degeneration occurring during PD.
Sheehan
J P
JP
Department of Neurological Surgery, University of Virginia, Charlottesville, USA.
Palmer
P E
PE
Helm
G A
GA
Tuttle
J B
JB
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D017209:Apoptosis; D015259:Dopamine Agents / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D009447:Neuroblastoma / Q000473:pathology*; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015259:Dopamine Agents; D015655:1-Methyl-4-phenylpyridinium