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The authors exposed mouse mesenchymal cells to lead in vitro and observed signaling changes in several proteins active in chondrogenesis: transforming growth factor-beta (TGF-[beta]), bone morphogenetic protein (BMP), activating protein 1 (AP-1), and nuclear factor kappa B (NF[kappa]B). OT-551 is a small molecule that acts through multiple pathways to downregulate the disease-induced overexpression of nuclear factor kappa B (NF-kB; a key player in human inflammatory disease) and to reduce oxidative stress. Lead exposure activates nuclear factor kappa B, activator protein- 1, c-Jun N-terminal kinase and caspases in the rat brain. |
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