Manganese-induced rat pheochromocytoma (PC12) cell death is independent of caspase activation

Roth, Jerome A.; Feng, Li; Walowitz, Jennifer L.; Browne, Richard W.

doi:10.1002/1097-4547(20000715)61:2<162::aid-jnr7>3.0.co;2-g

Cited by 82 publications

(27 citation statements)

References 43 publications

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“…Our data are in agreement with recent reports showing Mn-induced caspase-3 activation in neuronal and non-neuronal cell culture models (Schrantz et al, 1999;Chun et al, 2001;Hirata, 2002). However, caspase-independent cell death has also been reported after manganese exposure (Roth et al, 2000;Oubrahim et al, 2001;Stredrick et al, 2004); the different cell types or methodologies used in these studies may explain the incongruent results. In our study, we did not observe complete protection against Mn-induced cell death with Z-DEVD-FMK and suspect that the concentration of Z-DEVD-FMK (50 M) was insufficient to completely block Mn-induced cytotoxic cell death.…”

Section: Discussionsupporting

confidence: 91%

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

150

170

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Section: Discussionsupporting

confidence: 91%

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

150

170

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“…At 300 μM, MnCl 2 cell viability is 75%. This result is in good agreement with other studies of manganese cytotoxicity on PC12 cells as determined by MTT assay (18,19).…”

Section: Cytotoxicitysupporting

confidence: 93%

Manganese Accumulates within Golgi Apparatus in Dopaminergic Cells as Revealed by Synchrotron X-ray Fluorescence Nanoimaging

Carmona¹,

Devès²,

Roudeau³

et al. 2009

ACS Chem. Neurosci.

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Chronic exposure to manganese results in neurological symptoms referred to as manganism and is identified as a risk factor for Parkinson's disease. In vitro, manganese induces cell death in the dopaminergic cells, but the mechanisms of manganese cytotoxicity are still unexplained. In particular, the subcellular distribution of manganese and its interaction with other trace elements needed to be assessed. Applying synchrotron X-ray fluorescence nanoimaging, we found that manganese was located within the Golgi apparatus of PC12 dopaminergic cells at physiologic concentrations. At increasing concentrations, manganese accumulates within the Golgi apparatus until cytotoxic concentrations are reached resulting in a higher cytoplasmic content probably after the Golgi apparatus storage capacity is exceeded. Cell exposure to manganese and brefeldin A, a molecule known to specifically cause the collapse of the Golgi apparatus, results in the striking intracellular redistribution of manganese, which accumulates in the cytoplasm and the nucleus. These results indicate that the Golgi apparatus plays an important role in the cellular detoxification of manganese. In addition manganese exposure induces a decrease in total iron content, which could contribute to the overall neurotoxicity.

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“…The experiments described herein involve working concentrations up to 1000 μM for MnCl 2 and MnSO 4 , and up to 100 μM for MnPO 4 . The concentrations used in these studies are in line with many other experiments, i.e., Roth et al, (2000) and are representative of levels found in brains of non-human primates following exposure to manganese for 3 months (ranging from 35 to 350 μM; Suzuki et al, 1975).…”

Section: Striatal Tissue Experimentssupporting

confidence: 75%

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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Manganese-induced rat pheochromocytoma (PC12) cell death is independent of caspase activation

Cited by 82 publications

References 43 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

Manganese Accumulates within Golgi Apparatus in Dopaminergic Cells as Revealed by Synchrotron X-ray Fluorescence Nanoimaging

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

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