Determining the oxidation states of manganese in PC12 and nerve growth factor-induced PC12 cells

Karlene K. Gunter, Michael Aschner, Lisa M. Miller, Roman Eliseev, Jason Salter, Katie Anderson, Sean Hammond, Thomas E. Gunter

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Excessive brain Mn can produce toxicity with symptoms resembling parkinsonism. This syndrome, called "manganism," correlates with loss of dopamine in the striatum and cell death in the striatum and globus pallidus. A common hypothesis is that cell damage in Mn toxicity is caused by oxidation of important cell components by Mn3+. Determination of the amount of Mn3+ present, under a range of conditions, in neuronal cells and brain mitochondria represents an important step in evaluating the "damage through oxidation by Mn3+ hypothesis." In an earlier paper we used X-ray absorption near-edge structure (XANES) spectroscopy to determine the amount of Mn2+ and Mn3+ in brain mitochondria under a range of conditions. Here we extend the study to investigate the evidence for formation of Mn3+ through oxidation of Mn2+ by ROS in PC12 cells and in PC12 cells induced with nerve growth factor (NGF) to display a phenotype more like that of neurons. Although the results suggest that very small amounts of Mn3+ might be present at low Mn levels, probably in Mn superoxide dismutase, Mn3+ is not stabilized by complex formation in these cells and therefore does not accumulate to detectable amounts.

Original languageEnglish (US)
Pages (from-to)164-181
Number of pages18
JournalFree Radical Biology and Medicine
Volume39
Issue number2
DOIs
StatePublished - Jul 15 2005
Externally publishedYes

Keywords

  • Induced PC12 cells
  • Manganese oxidation states
  • Manganese toxicity
  • PC12 cells
  • XANES spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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