title: SO(2)-induced neurotoxicity is mediated by cyclooxygenases-2-derived prostaglandin E(2) and its downstream signaling pathway in rat hippocampal neurons.
abstract: Sulfur dioxide (SO(2)) pollution in atmospheric environment is involved in neurotoxicity and increased risk for hospitalization and mortality of many brain disorders; however, our understanding of the mechanisms by which SO(2) caused harmful insults on neurons remains elusive. Here, we show that SO(2) exposure produced a neuronal insult, and the neurotoxic effect was likely via stimulating cyclooxygenase-2 (COX-2) elevation by activation of nuclear factor-κB (NF-κB) activity and its acting on the promoter-distal NF-κB-binding site of COX-2 promoter. The action of SO(2) on elevating COX-2 ultimately appeared to be dependent on the increased production of arachidonic acid-derived prostaglandins, mainly prostaglandin E(2) (PGE(2)), and functioning of its EP2/4 receptors. Also, the molecular modulating process might be triggered by free radical attack from SO(2) metabolism in vivo and followed by activating cyclic adenosine monophosphate/protein kinase A pathway and enhancing probability of the release of glutamate, upregulating N-methyl-D-aspartic acid receptor expression and causing neuronal apoptosis. Our results reveal a mechanistic basis for exploring an association between SO(2) inhalation and increased risk for neurological disorders and opening up therapeutic approaches of treating, ameliorating, or preventing brain injuries resulting from SO(2) exposure in atmospheric polluting environment.
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China. sangnan_lgkcarl@yahoo.com.cn
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yun
authors.forename: Gao-yi
authors.initials: GY
authors.lastname: Yao
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Guang-ke
authors.initials: GK
authors.lastname: Li
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D020868:Gene Silencing; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013458:Sulfur Dioxide / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D000393:Air Pollutants; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D034741:RNA, Small Interfering; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013458:Sulfur Dioxide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone