Microglia and astroglia prevent oxidative stress-induced neuronal cell death: implications for aceruloplasminemia.
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.
Oshiro
Satoru
S
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
Kawamura
Ken-ichi
K
Zhang
Chun
C
Sone
Toshio
T
Morioka
Masaki S
MS
Kobayashi
Shin
S
Nakajima
Kazuyuki
K
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology*; D016923:Cell Death; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics; D018920:Coculture Techniques; D019610:Cytoprotection / Q000502:physiology; D004622:Embryo, Mammalian; D007501:Iron / Q000009:adverse effects / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D009410:Nerve Degeneration / Q000517:prevention & control*; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats
D007501:Iron; D002570:Ceruloplasmin