Microglia and astroglia prevent oxidative stress-induced neuronal cell death: Implications for aceruloplasminemia

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Article

Oshiro, Satoru¹  Kawamura, Ken-ichi²  Zhang, Chun¹  Sone, Toshio^3,5  Morioka, Masaki S.⁴  Nakajima, Kazuyuki⁶ 

[1] Daito Bunka Univ, Fac Sports & Hlth Sci, Dept Hlth Sci, Div Mol & Cellular Biochem, Higashi Matsuyama, Saitama 3558501, Japan

[2] NTC NIPPN Techno Cluster Inc, Dept Res & Dev, Tokyo 1690075, Japan

[3] Saitama Med Univ, Dept Allergy & Immunol, Moroyama, Saitama 3550495, Japan

[4] Tokyo Med & Dent Univ, Sch Biomed Sci, Dept Comp Biol, Tokyo 1138510, Japan

[5] Kirin Brewery Co Ltd, Div Pharmaceut, Tokyo 1508011, Japan

[6] Soka Univ, Inst Life Sci, Dept Neurochem, Tokyo 1928577, Japan

关键词: microglial;    astrocyte;    neuronal cell death;    oxidative stress;    neurodegenerative disorders;    aceruloplasminemia;   

DOI  :  10.1016/j.bbadis.2007.12.002

来源: Elsevier

【 摘 要 】

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 H2O2-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. (C) 2007 Elsevier B.V. All rights reserved.

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