Extracellular HMGB1 Released after Zinc-treatment Induces Neuronal Death in Primary Cortical Cultures.
- Author:
Chae Moon LIM
1
;
Jung Bin KIM
;
Ja Kyeong LEE
Author Information
1. Department of Anatomy and Center for Advanced Medical Education (BK21 project), Inha University School of Medicine, Inchon, Korea. jklee@inha.ac.kr
- Publication Type:Original Article
- Keywords:
Zinc;
HMGB1;
Primary cortical culture;
Neuronal cell death
- MeSH:
Cell Death;
Cell Survival;
Culture Media, Conditioned;
Cytokines;
Extracellular Space;
HMGB1 Protein;
Neurons;
Zinc
- From:Korean Journal of Anatomy
2008;41(1):89-96
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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 proinflammatory cytokines. Here, we the examined cytokine-like or signaling molecule-like function of extracellular HMGB1 in primary cortical 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.
