Manganese-Induced Cytotoxicity in Dopamine-Producing Cells

Stredrick, Denise L.; Stokes, Alan H.; Worst, Travis J.; Freeman, Willard M.; Johnson, E. A.; Lash, Lawrence H.; Aschner, Michael; Vrana, Kent E.

doi:10.1016/j.neuro.2003.08.006

Cited by 81 publications

(73 citation statements)

References 27 publications

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“…Based on these data and available literature, we concluded that excess dopamine in an ROS-rich environment may augment the oxidative insult by formation of highly cytotoxic radicals (Junn and Mouradian, 2001;Kitazawa et al, 2001), which may contribute to the enhanced susceptibility of dopaminergic neurons to MMT neurotoxicity. In agreement with our results, a recent study demonstrated that manganese is more toxic in catecholamine-producing cells than in noncatecholaminergic cells (Stredrick et al, 2004).…”

Section: Discussionsupporting

confidence: 93%

“…Depending on the level of exposure, blood manganese concentrations can increase from 10-to 200-fold (Hauser et al, 1996;Lucchini et al, 1999;Mergler et al, 1999;Woolf et al, 2002;McKinney et al, 2004). Normally, higher relative concentrations of manganese are required in cell culture studies, and the concentrations used in our studies are consistent with other studies (Hirata, 2002;Roth et al, 2002;Stredrick et al, 2004). Still, 300 M Mn was sufficient to induce apoptotic cell death in N27 cells, compared with the 0.6-1 mM concentration of Mn used in other cell types (Hirata, 2002;Roth et al, 2002).…”

Section: Discussionsupporting

confidence: 87%

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Protein Kinase Cδ Is a Key Downstream Mediator of Manganese-Induced Apoptosis in Dopaminergic Neuronal Cells

Latchoumycandane¹,

Anantharam²,

Kitazawa³

et al. 2004

J Pharmacol Exp Ther

153

170

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

Protein Kinase Cδ Is a Key Downstream Mediator of Manganese-Induced Apoptosis in Dopaminergic Neuronal Cells

Latchoumycandane¹,

Anantharam²,

Kitazawa³

et al. 2004

J Pharmacol Exp Ther

153

170

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“…NAC is an antioxidant and a precursor of GSH (Peristeris et al, 1992). NAC is also capable of crossing cellular membranes (Stredrick et al, 2004). On the other hand, GSH does not cross the cell membrane as readily as NAC (Deneke, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Stock solutions of (1) reduced L-glutathione (GSH), a major cellular antioxidant known to be depleted in the presence of Mn (Stredrick et al, 2004); (2) N-acetyl-L-cysteine (NAC), a GSH precursor and antioxidant reported to prevent apoptosis in neuronal cells (Ferrari et al, 1995); (3) catalase (CAT) and (4) superoxide dismutase (SOD), two major antioxidant enzymes which protect cells against oxidative damage (Rossman and Goncharova, 1998), were prepared in saline or HBHS. Final exposure working solutions were diluted in 1% HBHS.…”

Section: Preparation Of Pharmacological Reagentsmentioning

confidence: 99%

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

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Following combustion of fuel containing the additive methylcyclopentadienyl-manganesetricarbonyl (MMT), manganese phosphate (MnPO 4 ) and manganese sulfate (MnSO 4 ) are emitted in the atmosphere. Manganese chloride (MnCl 2 ), another Mn 2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO 4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl 2 or MnSO 4 ; antioxidants were partially protective. Also, both MnCl 2 and MnPO 4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO 4 will be more potent in forming aminochrome than MnCl 2 or MnSO 4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO 4 in particular, is the generation of reactive DA intermediates.

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“…Mn-induced Parkinsonism, also called manganism, has been associated with Mn mining and welding (Calne et al, 1994;Chia et al, 1993). Acute Mn 2+ toxicity results in symptoms similar to those seen in patients with PD, including rigidity, tremors, and bradykinesia (Stredrick et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Use of non-mammalian alternative models for neurotoxicological study

et al. 2008

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The field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals, and resource limitations and ethical concerns associated with testing using traditional mammalian species. National and international government agencies have defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and non-mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and the strong conservation between human and non-mammalian genomes allows for the dissection of the molecular pathways involved in neurotoxicological responses and neurological diseases using genetically tractable organisms. In this review, applications of four non-mammalian species, Zebrafish, cockroach, Drosophila, and Caenorhabditis elegans, in the investigation of neurotoxicology and neurological diseases are presented.

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Manganese-Induced Cytotoxicity in Dopamine-Producing Cells

Cited by 81 publications

References 27 publications

Protein Kinase Cδ Is a Key Downstream Mediator of Manganese-Induced Apoptosis in Dopaminergic Neuronal Cells

Protein Kinase Cδ Is a Key Downstream Mediator of Manganese-Induced Apoptosis in Dopaminergic Neuronal Cells

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Use of non-mammalian alternative models for neurotoxicological study

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