Determining the oxidation states of manganese in NT2 cells and cultured astrocytes

Excessive brain manganese (Mn) can produce a syndrome called "manganism", which correlates with loss of striatal dopamine and cell death in the striatum and globus pallidus. The prevalent hypothesis for the cause of this syndrome has been oxidation of cell components by the strong oxidizing agent, Mn³⁺, either formed by oxidation of intracellular Mn²⁺ or transported into the cell as Mn³⁺. We have recently used X-ray absorption near edge structure spectroscopy (XANES) to determine the oxidation states of manganese complexes in brain and liver mitochondria and in nerve growth factor (NGF)-induced and non-induced PC12 cells. No evidence was found for stabilization or accumulation of Mn³⁺ complexes because of oxidation of Mn²⁺ by reactive oxygen species in these tissues. Here we extend these studies of manganese oxidation state to cells of brain origin, human neuroteratocarcinoma (NT2) cells and primary cultures of rat astrocytes. Again we find no evidence for stabilization or accumulation of any Mn³⁺ complex derived from oxidation of Mn²⁺ under a range of conditions.