title: Metallothionein-III provides neuronal protection through activation of nuclear factor-kappaB via the TrkA/phosphatidylinositol-3 kinase/Akt signaling pathway.
abstract: 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 IkappaB, the nuclear translocation/accumulation and the transcriptional activity of nuclear factor-kappaB (NF-kappaB) in neuronal cells in a dose-dependent manner. The MT-III-induced antiapoptotic effects and increase in NF-kappaB activity were blocked by specific inhibitors of TrkA, phosphatidylinositol-3 kinase (PI3K), Akt, or NF-kappaB, indicating that MT-III provides neuronal protection by activating NF-kappaB through the TrkA/PI3K/Akt signaling pathway.
authors.affiliation: Department of Pharmacy and Research Center for Proteineous Materials, College of Pharmacy, Chosun University, Gwangju, South Korea.
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Chul Yung
authors.initials: CY
authors.lastname: Choi
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yeo
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D000090023:Metallothionein 3; D016328:NF-kappa B / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D045304:Cytochromes c; D000090023:Metallothionein 3; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D020917:Receptor, trkA