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Related Experiment Videos

Manganese oxidation state and its implications for toxicity.

Stephen H Reaney1, Catherine L Kwik-Uribe, Donald R Smith

  • 1Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA. stevereaney@hotmail.com

Chemical Research in Toxicology
|September 17, 2002
PubMed
Summary

Manganese oxidation state impacts cellular uptake and toxicity. Exposure to manganese(III) significantly increased cellular manganese accumulation and inhibited aconitase activity more than manganese(II).

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Area of Science:

  • Environmental toxicology
  • Biochemistry
  • Inorganic chemistry

Background:

  • Manganese (Mn) is essential for mammalian development but toxic at high levels.
  • Mn's biological functions depend on its oxidation state (e.g., Mn(II), Mn(III)).
  • The impact of Mn oxidation state on cellular uptake and toxicity is poorly understood.

Purpose of the Study:

  • Investigate how Mn oxidation state affects cellular uptake and toxicity.
  • Examine the dynamics of EPR-measurable Mn(II) in plasma and cell lysates.
  • Assess the effects of Mn(II) versus Mn(III) exposure on cellular aconitase activity and Mn uptake.

Main Methods:

  • Exposed fresh human plasma and PC12 cell lysates to manganese(II) chloride and manganese(III) pyrophosphate.
  • Measured EPR-detectable Mn(II) dynamics.

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  • Assessed total cellular aconitase activity and cellular Mn uptake in intact PC12 cells.
  • Main Results:

    • In vitro exposure of plasma/lysates to Mn(II) or Mn(III) yielded similar EPR-measurable Mn(II).
    • Mn(III) exposure significantly inhibited cellular aconitase activity more than Mn(II).
    • Intact PC12 cells accumulated significantly more Mn when exposed to Mn(III) compared to Mn(II).

    Conclusions:

    • Mn speciation is dynamic in biological systems.
    • The oxidation state of manganese is crucial in mediating cellular toxicity.
    • Elevated environmental exposure to various Mn oxidation states warrants concern.