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Manganese oxidation state mediates toxicity in PC12 cells
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. stevereaney@hotmail.com
Toxicology and Applied Pharmacology
|June 1, 2005
Summary
Manganese oxidation state significantly impacts cellular uptake and toxicity. Mn(III) increased cellular manganese more than Mn(II), causing distinct toxic effects and neurotransmitter level changes.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- The impact of manganese (Mn) oxidation state on cellular manganese uptake and toxicity remains unclear.
- Understanding these differences is crucial for assessing Mn-related health risks.
Purpose of the Study:
- To investigate the differential effects of manganese(II) and manganese(III) on cellular manganese levels, viability, and specific cellular functions.
- To elucidate the role of manganese oxidation state in mediating manganese-induced cytotoxicity.
Main Methods:
- PC12 cells were exposed to varying concentrations of Mn(II)-chloride and Mn(III)-pyrophosphate.
- Cellular manganese levels, viability (trypan blue exclusion, ATP), cytotoxicity (LDH), and protein levels (H-ferritin, TfR, MnSOD, CuZnSOD) were measured.
- Neurotransmitter levels (dopamine, serotonin) were also assessed.
Main Results:
- Mn(III) exposures resulted in 2- to 5-fold higher cellular manganese levels than equimolar Mn(II) exposures.
- Both Mn(II) and Mn(III) decreased cell viability and ATP at high concentrations (150-200 microM).
- Mn(III) increased LDH activity at lower concentrations than Mn(II), and differential effects on dopamine, serotonin, H-ferritin, TfR, and MnSOD were observed.
Conclusions:
- The oxidation state of manganese exposure plays a critical role in mediating manganese cytotoxicity.
- Differential cellular responses to Mn(II) versus Mn(III) suggest oxidation state-specific mechanisms of toxicity beyond simple cellular manganese levels.