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KMID : 0363720080410010089
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Korean Journal of Anatomy
2008 Volume.41 No. 1 p.89 ~ p.96
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Extracellular HMGB1 Released after Zinc-treatment Induces Neuronal Death in Primary Cortical Cultures
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Lim Chae-Moon
Lee Ja-kyung
Kim Jung-Bin
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Abstract
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As a nonhistone DNA-binding protein, high mobility group box 1 (HMGB1) is released in large amounts into the extracellular space immediately after ischemic insult and plays a role in the release of proinflammatorycytokines. Here, we the examined cytokine-like or signaling molecule-like function of extracellular HMGB1 in primarycortical cultures. We found that a large amount of HMGB1 was released following zinc-induced neuronal cell death in primary cortical cultures and that this extracellular HMGB1 might aggravate neuronal damage. The conditioned media collected from zinc-treated primary cortical cultures decreased neuronal cell survival to 69.6± 1.4% of control values when added to fresh primary cortical cultures. In contrast, treatment with HMGB1-depleted conditioned media produced by cultures treated with an HMGB1 siRNA-expression vector suppressed the induction of neuronal death. A mutant HMGB1 siRNA-expression vector did not suppress the induction of neuronal death, demonstrating a role of HMGB1 in neuronal death. Moreover, HMGB1-depletion in media conditioned by cotreatment with anti-HMGB1 antibody or with anti-RAGE antibody, a potential receptor for HMGB1, recovered neuronal cell survival to 81.0± 4.0% and 79.0±4.0%, respectively, when added to fresh primary cortical cultures. These results indicate that extracellular HMGB1 released after zinc treatment induces neuronal death, which might aggravate zinc toxicity.
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KEYWORD
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Zinc, HMGB1, Primary cortical culture, Neuronal cell death
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