Immortalization of embryonic mesencephalic dopaminergic neurons by somatic cell fusion

Choi, Hae-Jin; Won, Lisa; Kontur, Paul J.; Hammond, David N.; Fox, Aaron P.; Wainer, Bruce H.; Hoffmann, Philip C.; Heller, Alfred

doi:10.1016/0006-8993(91)90661-e

Cited by 208 publications

(216 citation statements)

References 44 publications

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“…Cell Culture-The MN9D dopaminergic cell line originates from fusion of rostral mesencephalic neurons from embryonic C57BL/BJ (embryonic day 14 mice) with N18TG2 neuroblastoma cells (27). MN9D cells were grown in a high glucose (4500 mg/liter) Dulbecco's modified Eagle's medium (Sigma) containing 10% Tet-approved fetal bovine serum (Invitrogen), 3.7 g liter Ϫ1 NaHCO 3 and 4 mM L-glutamine in a 5% CO 2 atmosphere at 37°C.…”

Section: Chemicals and Biological Reagents-1-methyl-4-phenyl Tetrahydmentioning

confidence: 99%

The Peptidyl-prolyl Isomerase Pin1 Up-regulation and Proapoptotic Function in Dopaminergic Neurons

Ghosh

Saminathan

Kanthasamy

et al. 2013

Journal of Biological Chemistry

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Background: Pin1 regulates several signaling proteins by isomerizing the cis/trans conformation of the Ser(P)-Pro peptide bond. Results: Pin1 is up-regulated in dopaminergic neurons in cell culture, animal models, and human PD brains. Pin1 inhibition protects dopaminergic neurons in PD models. Conclusion: Pin1 up-regulation plays a proapoptotic function in PD. Significance: Pin1 inhibition may be a viable translational strategy in PD.

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Section: Chemicals and Biological Reagents-1-methyl-4-phenyl Tetrahydmentioning

confidence: 99%

The Peptidyl-prolyl Isomerase Pin1 Up-regulation and Proapoptotic Function in Dopaminergic Neurons

Ghosh

Saminathan

Kanthasamy

et al. 2013

Journal of Biological Chemistry

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“…To study the cellular mechanisms of rotenone-induced dopaminergic neuronal degeneration, we therefore developed a novel cellular model derived from immortalized midbrain MN9D cells (15), a dopaminergic neuronal cell line that has been extensively characterized as a model of dopaminergic neurons (16 -19). Using sodium butyrate (NaBu) (20) to differentiate MN9D cells and cells from a related, immortalized, non-dopaminergic midbrain neuronal cell line (MN9X cells), we have produced dopaminergic and non-dopaminergic cell cultures that can be maintained in vitro for weeks without pro-liferation.…”

mentioning

confidence: 99%

Distinct Mechanisms of Neurodegeneration Induced by Chronic Complex I Inhibition in Dopaminergic and Non-dopaminergic Cells

Kweon¹,

Marks²,

Krencik³

et al. 2004

Journal of Biological Chemistry

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The pathogenesis underlying the selective degeneration of dopaminergic neurons in Parkinson's disease (PD) 1 is not fully defined, but multiple lines of evidence implicate mitochondrial dysfunction. Thus, defects in complex I of the mitochondrial respiratory chain in the substantia nigra and evidence of oxidative stress have been noted in the brains of PD patients (1, 2). PD is also associated with exposure to pesticides (3, 4), many of which are either oxidants or mitochondrial toxins. Rapid onset of Parkinsonism in young adults following injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (5) occurs through its active metabolite, 1-methyl-4-phenylpyridinium, an inhibitor of mitochondrial complex I (6), potentially by depleting energy stores and inducing oxidative stress (7,8).Complex I is specifically and irreversibly inhibited by the neurotoxin rotenone, a hydrophobic pesticide epidemiologically linked to PD. Continuous, systemic, in vivo infusion of 2-3 mg/kg/day rotenone in rats over weeks produces relatively selective nigrostriatal dopaminergic neurodegeneration, with formation of ubiquitin-and ␣-synuclein-positive inclusions (9, 10). This low dose paradigm results in about 75% inhibition of complex I activity, and corresponds to a brain concentration of 20 -30 nM (9, 10). However, although these studies establish the principle that complex I dysfunction leads to degeneration in dopaminergic neurons, consistent levels of functional deficits related to complex I dysfunction have been difficult to reproduce (11). Accordingly, this in vivo model has not lent itself easily to the study of the mechanism of rotenone toxicity (12). Similarly, the use of primary cultures of dopaminergic neurons to study mechanisms of rotenone-induced neurodegeneration has been limited: short term, nanomolar rotenone administration in primary cultures of dopaminergic neurons does not produce selective dopaminergic damage (13). In addition, primary cultures contain a mixture of dopaminergic and nondopaminergic neurons and therefore do not lend themselves to molecular and biochemical analyses. The use of existing cell lines to study the effects of chronic rotenone exposure (14) also has shortcomings. Most cell lines do not exhibit robust dopaminergic phenotypes. In addition, the high rate of proliferation that characterize these cell lines confound the assessment of cellular susceptibility to rotenone, because proliferating cells may replace those that have succumbed to rotenone, and chronic exposure may lead to the selection of cells that become resistant to rotenone toxicity.To study the cellular mechanisms of rotenone-induced dopaminergic neuronal degeneration, we therefore developed a novel cellular model derived from immortalized midbrain MN9D cells (15), a dopaminergic neuronal cell line that has been extensively characterized as a model of dopaminergic neurons (16 -19). Using sodium butyrate (NaBu) (20) to differentiate MN9D cells and cells from a related, immortalized, non-dopaminergic midbrain neuronal cell line (MN9X ...

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“…Using a dopaminergic neuronal cell line, MN9D, derived from murine mesencephalon (21,22), several cDNA fragments that corresponded to putatively upregulated or downregulated transcripts were isolated following 200 M MPP ϩ treatment. Interestingly, sequence analysis revealed that two of the cDNA species matched the sequences of mitochondrially encoded cytochrome c oxidase subunit 3 (COX III) and ATPase subunit 6 (ATPase 6) which are catalytic components of multimeric cytochrome c oxidase and ATP synthase complex, respectively (23,24).…”

mentioning

confidence: 99%

MPP+ Downregulates Mitochondrially Encoded Gene Transcripts and Their Activities in Dopaminergic Neuronal Cells: Protective Role of Bcl-2

Kim

Yoon

Lee

et al. 2001

Biochemical and Biophysical Research Communications

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Immortalization of embryonic mesencephalic dopaminergic neurons by somatic cell fusion

Cited by 208 publications

References 44 publications

The Peptidyl-prolyl Isomerase Pin1 Up-regulation and Proapoptotic Function in Dopaminergic Neurons

The Peptidyl-prolyl Isomerase Pin1 Up-regulation and Proapoptotic Function in Dopaminergic Neurons

Distinct Mechanisms of Neurodegeneration Induced by Chronic Complex I Inhibition in Dopaminergic and Non-dopaminergic Cells

MPP+ Downregulates Mitochondrially Encoded Gene Transcripts and Their Activities in Dopaminergic Neuronal Cells: Protective Role of Bcl-2

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