Microglia and astroglia prevent oxidative stress-induced neuronal cell death: implications for aceruloplasminemia |
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Authors: | Oshiro Satoru Kawamura Ken-ichi Zhang Chun Sone Toshio Morioka Masaki S Kobayashi Shin Nakajima Kazuyuki |
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Institution: | Division of Molecular and Cellular Biochemistry, Department of Health Science, Faculty of Sports and Health Sciences, Daito Bunka University, 560 Iwadono, Higashi-matsuyama, Saitama 355-8501, Japan. soshiro@ic.daito.ac.jp |
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Abstract: | We partially characterized the transferrin-independent iron uptake (Tf-IU) of neuronal and glial cells in the previous report. In the present study, we further examined a mechanism of which glial cells protect neuronal cells against iron stress using neuron-microglia (N-MG) and neuron-astrocyte (N-AS) co-cultures. When each solely purified cell was treated with iron citrate, cell death occurred in N and MG. However, AS proliferated under the same condition. Both N-MG and N-AS co-cultures were effective in resistance to excessive iron. The total and specific Tf-IU activities of N-MG co-cultures similar to those of N did not increase in a density-dependent manner. Contrarily, the total activity of AS was extremely high and the specific activity was extremely low as a result of proliferation. Regarding of effect of co-cultures on H(2)O(2)-induced cell death, N-MG co-cultures were less effective, but N-AS co-cultures were more effective in protecting N from the oxidative stress. These results suggest that N-MG co-cultures suppress the Tf-IU and N-AS co-cultures stimulate AS proliferation to protect neuronal cells. Brain cells from aceruloplasminemia with mutations in the ceruloplasmin gene take up iron by Tf-IU. Therefore, the different mechanisms of neuronal cell protection by MG and AS may explain the pathophysiological observations in the brains of patient with aceruloplasminemia. |
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