Title: Lead induces COX-2 expression in glial cells in a NFAT-dependent, AP-1/NFκB-independent manner.
Authors: Wei, Jinlong; Du, Kejun; Cai, Qinzhen; Ma, Lisha; Jiao, Zhenzhen; Tan, Jinrong; Xu, Zhou; Li, Jingxia; Luo, Wenjin; Chen, Jingyuan; Gao, Jimin; Zhang, Dongyun; Huang, Chuanshu
Published In Toxicology, (2014 Nov 5)
Abstract: Epidemiologic studies have provided solid evidence for the neurotoxic effect of lead for decades of years. In view of the fact that children are more vulnerable to the neurotoxicity of lead, lead exposure has been an urgent public health concern. The modes of action of lead neurotoxic effects include disturbance of neurotransmitter storage and release, damage of mitochondria, as well as induction of apoptosis in neurons, cerebrovascular endothelial cells, astroglia and oligodendroglia. Our studies here, from a novel point of view, demonstrates that lead specifically caused induction of COX-2, a well known inflammatory mediator in neurons and glia cells. Furthermore, we revealed that COX-2 was induced by lead in a transcription-dependent manner, which relayed on transcription factor NFAT, rather than AP-1 and NFκB, in glial cells. Considering the important functions of COX-2 in mediation of inflammation reaction and oxidative stress, our studies here provide a mechanistic insight into the understanding of lead-associated inflammatory neurotoxicity effect via activation of pro-inflammatory NFAT3/COX-2 axis.
PubMed ID: 25193092
MeSH Terms: Animals; Cyclooxygenase 2/biosynthesis*; Cyclooxygenase 2/genetics; Dose-Response Relationship, Drug; Endothelial Cells/drug effects; Endothelial Cells/enzymology; Enzyme Induction; Inflammation Mediators/metabolism; Lead Poisoning, Nervous System/enzymology; Lead Poisoning, Nervous System/etiology*; Lead Poisoning, Nervous System/genetics; Lead/toxicity*; Mice; NF-kappa B/metabolism*; NFATC Transcription Factors/genetics; NFATC Transcription Factors/metabolism*; Neural Stem Cells/drug effects; Neural Stem Cells/enzymology; Neuroglia/drug effects*; Neuroglia/enzymology; Neurons/drug effects; Neurons/enzymology; PC12 Cells; RNA, Messenger/biosynthesis; Rats; Signal Transduction/drug effects; Time Factors; Transcription Factor AP-1/metabolism*; Transcription, Genetic/drug effects; Transfection; Up-Regulation