1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism

Storch, Alexander; Kaftan, Anne; Burkhardt, Katrin; Schwarz, Johannes

doi:10.1016/s0006-8993(99)02272-6

Cited by 92 publications

(58 citation statements)

References 48 publications

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“…Furthermore, cell death in MN9D cells induced by 6-OHDA was not accompanied by a decrease in ATPase 6 transcripts or in the intracellular content of ATP. This finding is somewhat in agreement with the recent report that cell death induced by 6-OHDA in human SH-SY5Y dopaminergic neuroblastoma is independent of mitochondrial energy metabolism (18,19). Taken together, these findings further expand previous suggestions that distinct pathways may be involved in MPP ϩ or 6-OHDA at least in cultured dopaminergic neurons (15)(16)(17).…”

Section: Discussionsupporting

confidence: 92%

“…Recent studies also raise the possibility that cell death induced by MPP ϩ or 6-OHDA in culture models of dopaminergic neurons may recruit a distinct death pathway that diverges at a very early stage thereby leading to a specific mode of cell death (15)(16)(17)(18)(19). For example, MPP ϩ seems to induce caspase-independent necrosis while 6-OHDA leads to caspase-dependent apoptosis in cultures of dopaminergic neurons.…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

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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“…ATP depletion has also been observed as a primary consequence of MPP ϩ toxicity in hepatocytes (35), brain mitochondria (36), and mouse striatum (37,38), and providing metabolites of glycolysis attenuates it (39). Similarly, supplementation with D-␤-hydroxybutyrate, as well as glucose, protects neurons from MPP ϩ toxicity in vitro and in vivo (34,40,41). Accordingly, the importance of bioenergetics in the pathogenesis of PD warrants further investigation (42).…”

Section: Discussionmentioning

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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“…In this investigation several neurotoxins were chosen as oxidative stressors. Salsolinol has been reported to cause oxidative stress by increasing ROS levels, decreasing ATP and glutathione levels in SH-SY5Y cell line by inhibiting mitochondrial complex-I and complex-II enzyme activities, tyrosine hydroxylase and monoamine oxidase [7,19,20]. Cell death was not inhibited by the addition of antioxidants such as -tocopherol or the water-soluble vitamin E analogue-Trolox C, however nicotine and donepezil restored cell survival, indicating that in the salsolinol toxicity nicotinic receptors could be involved [21,22].…”

Section: Discussionmentioning

confidence: 99%

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

Wszelaki¹,

Melzig²

2013

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Oxidative stress has been implicated as one of the causes in cell death in many neurodegenerative disorders. Due to antioxidative properties in vitro, the use of flavonoids and other polyphenolic compounds synthesised by plants are considered to be a promising strategy to prevent Alzheimer's disease and Parkinsons's disease. In the present study, we tested protective effects of some polyphenols and sodium pyruvate on 6-hydroxydopamine (6-OHDA), salsolinol and 3-hydroxykynurenine (3-HK) induced neurotoxicity in human neuroblastoma SH-SY5Y cells. We found that luteolin prevented from 6-OHDA and 3-HK induced cell viability reduction and that one of the mechanisms involved in the neuroprotective process was the ability to increase the level of cellular ATP. However, luteolin was ineffective against salsolinol-induced toxicity. Neither pre-treatment with flavonoids nor simultaneous addition had any protective effects on 6-OHDA, salsolinol or 3-HK induced neurotoxicity. Interestingly, both pre-treatment and co-treatment with pyruvate provided protection against 6-OHDA, salsolinol or 3-HK induced toxicity. Moreover, luteolin and sodium pyruvate, administered together, acted additively, so to achieve the same effect, lower concentrations were needed. The ability of luteolin and sodium pyruvate to reduce toxicity of 6-OHDA and 3-HK in SH-SY5Y cells may be related to two different neuroprotective mechanisms and the capability to penetrate into the cell.

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1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism

Cited by 92 publications

References 48 publications

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

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

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

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

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