Apoptosis is induced by 1-methyl-4-phenylpyridinium ion (MPP+) in ventral mesencephalic-striatal co-culture in rat

Mochizuki, Hideki; Nakamura, N; Nishi, Katsunori; Mizuno, Yoshikuni

doi:10.1016/0304-3940(94)90271-2

Cited by 138 publications

(52 citation statements)

References 12 publications

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“…MPP ϩ enters the dopaminergic neuron where it inhibits mitochondrial complex I, precipitating severe ATP depletion (Ramsay et al, 1986;Hoppel et al, 1987;Mizuno et al, 1987). This energy crisis initiates a chain of events, culminating in the inability to release sufficient amounts of dopamine (Wesemann et al, 1993;Bezard et al, 2000), locomotor deficits (Chassain et al, 2001;Tillerson et al, 2002), and, ultimately, apoptosis of tyrosine hydroxylase (TH)-positive neurons in the SN (Dipasquale et al, 1991;CruzSanchez et al, 1993;Mochizuki et al, 1994;Ali et al, 1998;Brooks et al, 1999;Mandir et al, 1999;Viswanath et al, 2001). MPP ϩ toxicity stimulates the generation of oxygen-free radicals and nitric oxide (NO), which can promote oxidative damage to macromolecules including cellular proteins implicated in PD pathogenesis such as TH and ␣-synuclein (Pennathur et al, 1999;Souza et al, 2000;Paxinou et al, 2001;Park et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra

Miller¹,

Callahan²,

Casaceli³

et al. 2004

J. Neurosci.

101

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Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra

Miller¹,

Callahan²,

Casaceli³

et al. 2004

J. Neurosci.

101

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“…However, the type of cell death and its associated mechanisms induced by this neurotoxin are still controversial. For example, although several lines of evidence have indicated that cells treated with MPTP or MPP ϩ exhibit typical apoptotic features, the cell types tested are not neurons nor has it been clearly demonstrated that the cells dying of apoptosis are indeed dopaminergic neurons (6,13,14,26,36). In contrast, it has been suggested that intracellular ATP levels determine whether a cell dies by apoptosis or necrosis (8).…”

Section: Introductionmentioning

confidence: 99%

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

Choi

Canzoniero

Sensi

et al. 1999

Experimental Neurology

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Section: Abstract: Parkinson's Disease; Caspase-8; Apoptosis; Necrosmentioning

confidence: 99%

“…Apoptosis is also observed in in vivo and in vitro models of PD based on the toxicity of 1-methyl-4-phenylpyridinium (MPP ϩ ) and 6-hydroxydopamine for DA neurons (Hartley et al, 1994;Mochizuki et al, 1994;Tatton and Kish, 1997;Dodel et al, 1998Dodel et al, , 1999Ochu et al, 1998;Spooren et al, 1998;Takai et al, 1998;Lotharius et al, 1999). Apoptosis may reflect a primary disease mechanism in PD, i.e., inappropriate excessive apoptosis, or appropriate apoptosis as the consequence of cell damage subsequent to oxidative stress, iron accumulation, mitochondrial complex I insufficiency, excitotoxicity, nitric oxide formation, inflammatory processes, and other cellular abnormalities described in PD (Marsden and Olanow, 1998).…”

mentioning

confidence: 99%

Caspase-8 Is an Effector in Apoptotic Death of Dopaminergic Neurons in Parkinson's Disease, But Pathway Inhibition Results in Neuronal Necrosis

et al. 2001

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Caspase-8 is a proximal effector protein of the tumor necrosis factor receptor family death pathway. In the present human postmortem study, we observed a significantly higher percentage of dopaminergic (DA) substantia nigra pars compacta neurons that displayed caspase-8 activation in Parkinson's disease (PD) patients compared with controls. In an in vivo experimental PD model, namely subchronically 1,2,3,6-tetrahydropyridinetreated mice, we also show that caspase-8 is indeed activated after exposure to this toxin early in the course of cell demise, suggesting that caspase-8 activation precedes and is not the consequence of cell death. However, cotreatment of 1-methyl-4-phenylpyridinium-intoxicated primary DA cultures with broad-spectrum and specific caspase-8 inhibitors did not result in neuroprotection but seemed to trigger a switch from apoptosis to necrosis. We propose that this effect is related to ATP depletion and suggest that the use of caspase inhibitors in pathologies linked to intracellular energy depletion, such as PD, should be cautiously evaluated. Key words: Parkinson's disease; caspase-8; apoptosis; necrosis; ATP; MPTPSeveral recent human postmortem studies have suggested that dopaminergic (DA) neurons die by apoptosis in Parkinson's disease (PD) (for review, see . Apoptosis is also observed in in vivo and in vitro models of PD based on the toxicity of 1-methyl-4-phenylpyridinium (MPP ϩ ) and 6-hydroxydopamine for DA neurons (Hartley et al., 1994;Mochizuki et al

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Apoptosis is induced by 1-methyl-4-phenylpyridinium ion (MPP+) in ventral mesencephalic-striatal co-culture in rat

Cited by 138 publications

References 12 publications

Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra

Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra

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

Caspase-8 Is an Effector in Apoptotic Death of Dopaminergic Neurons in Parkinson's Disease, But Pathway Inhibition Results in Neuronal Necrosis

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