title: Endogenous 2-Arachidonoylglycerol Alleviates Cyclooxygenases-2 Elevation-Mediated Neuronal Injury From SO2 Inhalation via PPARγ Pathway.
abstract: Although the health effects of sulfur dioxide (SO2) pollution in the atmospheric environment are not new, epidemiological studies and parallel experimental investigations indicate that acute SO2 exposure causes glutamate-mediated excitotoxicity and even contributes to the outcome of cerebral ischemia. Additionally, the free radical-related inflammatory responses are responsible for neuronal insults and consequent brain disorders. However, few medications are available for preventing the inflammatory responses and relieving the subsequent harmful insults from SO2 inhalation. Here, we show that endocannabinoid 2-arachidonoylglycerol (2-AG) prevents neurotoxicity from SO2 inhalation by suppressing cyclooxygenase-2 (COX-2) overexpression, and this action appears to be mediated via cannabinoid receptor 1 (CB1)-dependent mitogen-activated protein kinase/nuclear factor κB (NF-κB) signaling pathways. Furthermore, CB1-dependent peroxisome proliferator activated receptor γ (PPARγ) expression was an important modulator of the 2-AG-mediated resolution on NF-κB-coupled COX-2 elevation in response to SO2 neuroinflammation. This finding provides evidence of a possible therapeutic effect of endogenous 2-AG regulation for protecting against neurological dysfunction from SO2 inhalation in polluted areas.
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.
authors.forename: Ben
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Chen
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yun
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.
authors.forename: Guangke
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China sangnan@sxu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000032:analysis; D063388:Endocannabinoids / Q000378:metabolism / Q000502:physiology*; D005989:Glycerides / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013458:Sulfur Dioxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D013458:Sulfur Dioxide; C094503:glyceryl 2-arachidonate; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: cyclooxygenase-2 (COX-2); endocannabinoid 2-arachidonoylglycerol (2-AG); neuroinflammation; peroxisome proliferator activated receptor γ (PPARγ); sulfur dioxide (SO2)