Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

“…In contrast to previous studies [31,32], our results indicated the involvement of the apoptotic pathway in MPP + -induced cell death in MN9D. We found no significant increase in LDH liberation by MPP + -treated MN9D cells in comparison to the untreated cells, hence ruling out necrosis as a main mode of cell death that contributed to the overall cell loss.…”

“…The dopaminergic characteristics of our MN9D cells were consistent with early reports stating that the parental cell line could synthesize, release and take up dopamine [25,30]. MN9D cells have been used in several laboratories as a model for studying PD [12,[31][32][33][34][35][36] and are a useful system for investigating the specific roles of cell death pathways as well as to identify the nuclear/cytoplasmic components which participate in these pathways.…”

“…The discrepancies between previous results and ours may be attributed to the difference in dosage and duration of MPP + treatment used in the experiments. Choi et al [31,32] treated the cells with 25-100 µM MPP + over 12-36 h, while we applied the dosage of 500 µM MPP + under serum-free conditions over 24 h. To substantiate our claims, MPP + -treated cells were stained with acridine orange/ethidium bromide and we detected a high percentage of chromatin condensation indicative of apoptosis ( fig. 2B).…”

Microarray Expression Profiling Identifies Early Signaling Transcripts Associated with 6-OHDA-Induced Dopaminergic Cell Death

“…Earlier studies have shown that MPP + and 6-OHDA trigger morphologically distinct types of cell death in dopaminergic cells, although both depend on new protein synthesis (3,4,12,15). Using microarray analysis to determine the underlying patterns of gene expression occurring in response to these parkinsonian mimetics, we previously reported that 6-OHDA triggered multiple signaling pathways associated with cellular stress and unfolded protein response, whereas MPP + seemed to activate a more limited stress response (15).…”

Metabolic effects of 1-methyl-4-phenylpyridinium (MPP+) in primary neuron cultures

“…Related components of the injury mechanism may include increased oxidative stress (Adams et al, 1989;Kovacic et al, 1991;Hussain et al, 1999), potentially involving hydroxyl radical formation via auto-oxidation of released dopamine (Obata, 1999;Rose et al, 1999). Cell loss is associated with DNA fragmentation (DiPasquale et al, 1991), although there is evidence in some models that MPP ϩ -induced cell death may be independent of Bax expression or caspase activation typically associated with apoptotic mechanisms (Choi et al, 1999).…”