Journal Article

Metallothionein-III Provides Neuronal Protection through Activation of Nuclear Factor-κB via the TrkA/Phosphatidylinositol-3 kinase/Akt Signaling Pathway

Hyung Gyun Kim, Yong Pil Hwang, Eun Hee Han, Chul Yung Choi, Chang-Yeol Yeo, Jin Young Kim, Kwang Youl Lee and Hye Gwang Jeong

in Toxicological Sciences

Volume 112, issue 2, pages 435-449
Published in print December 2009 | ISSN: 1096-6080
Published online September 2009 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfp230
Metallothionein-III Provides Neuronal Protection through Activation of Nuclear Factor-κB via the TrkA/Phosphatidylinositol-3 kinase/Akt Signaling Pathway

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Metallothionein (MT)-III is associated with resistance to neuronal injury. However, the underlying mechanism for its effects is unclear. The present study investigated the mechanisms of MT-III protection of neuronal cells from hypoxia or DNA damage–induced cell death. MT-III reduced the hydrogen peroxide– or DNA damage–induced effects on neuronal cells, including the cell death, the activation of caspase-3 and -9, and the release of mitochondrial cytochrome c to the cytoplasm in a dose-dependent manner. MT-III also increased the activation of Akt, the phosphorylation and degradation of IκB, the nuclear translocation/accumulation and the transcriptional activity of nuclear factor-κB (NF-κB) in neuronal cells in a dose-dependent manner. The MT-III–induced antiapoptotic effects and increase in NF-κB activity were blocked by specific inhibitors of TrkA, phosphatidylinositol-3 kinase (PI3K), Akt, or NF-κB, indicating that MT-III provides neuronal protection by activating NF-κB through the TrkA/PI3K/Akt signaling pathway.

Keywords: metallothionein-III; neuronal protection; NF-κB; TrkA; Akt

Journal Article.  7707 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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