title: Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum.
abstract: To study central nervous system airborne PM related subchronic toxicity, SD male rats were exposed for eight weeks to either coarse (32 μg/m³), fine (178 μg/m³) or ultrafine (107 μg/m³) concentrated PM or filtered air. Different brain regions (olfactory bulb, frontal cortex, striatum and hippocampus), were harvested from the rats following exposure to airborne PM. Subsequently, prooxidant (HO-1 and SOD-2), and inflammatory markers (IL-1β and TNFα), apoptotic (caspase 3), and unfolded protein response (UPR) markers (XBP-1S and BiP), were also measured using real-time PCR. Activation of nuclear transcription factors Nrf-2 and NF-κB, associated with antioxidant and inflammation processes, respectively, were also analyzed by GSMA. Ultrafine PM increased HO-1 and SOD-2 mRNA levels in the striatum and hippocampus, in the presence of Nrf-2 activation. Also, ultrafine PM activated NF-κB and increased IL-1β and TNFα in the striatum. Activation of UPR was observed after exposure to coarse PM through the increment of XBP-1S and BiP in the striatum, accompanied by an increase in antioxidant response markers HO-1 and SOD-2. Our results indicate that exposure to different size fractions of PM may induce physiological changes (in a neuroanatomical manner) in the central nervous system (CNS), specifically within the striatum, where inflammation, oxidative stress and UPR signals were effectively activated.
authors.affiliation: Department of Toxicology, CINVESTAV-IPN, México, DF, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Guerra
authors.forename: E
authors.initials: E
authors.lastname: Vera-Aguilar
authors.forename: M
authors.initials: M
authors.lastname: Uribe-Ramirez
authors.forename: G
authors.initials: G
authors.lastname: Gookin
authors.forename: J
authors.initials: J
authors.lastname: Camacho
authors.forename: A R
authors.initials: AR
authors.lastname: Osornio-Vargas
authors.forename: V
authors.initials: V
authors.lastname: Mugica-Alvarez
authors.forename: R
authors.initials: R
authors.lastname: Angulo-Olais
authors.forename: A
authors.initials: A
authors.lastname: Campbell
authors.forename: J
authors.initials: J
authors.lastname: Froines
authors.forename: T M
authors.initials: TM
authors.lastname: Kleinman
authors.forename: A
authors.initials: A
authors.lastname: De Vizcaya-Ruiz
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002491:Central Nervous System Agents / Q000737:chemistry / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008800:Mexico; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D000071717:X-Box Binding Protein 1; D000099156:Superoxide Dismutase 2
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D002491:Central Nervous System Agents; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing); D009419:Nerve Tissue Proteins; D052638:Particulate Matter; D000071701:Regulatory Factor X Transcription Factors; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D000099156:Superoxide Dismutase 2; C000605545:Xbp1 protein, rat; C491523:Hmox1 protein, rat
keywords: ATF6; BiP; Central nervous system; GSMA; HO-1; IL-1β; IRE1α; Inflammation; NF-κB; Nrf-2; Oxidative stress; PAHs; PERK; PM; Particulate matter; SOD; Striatum; TNFα; UPR; Unfolded protein response; VACES; X-box binding protein 1; XBP-1; XBP-1 spliced form; XBP-1 unspliced form; XBP-1S; XBP-1U; activating transcription factor 6; eukaryotic translation initiation factor 2-alpha kinase 3; gel shift mobility assay; heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa); heme oxygenase 1; inositol-requiring protein 1; interleukin 1 beta; nuclear factor (erythroid-derived 2)-like 2; nuclear factor kappa-light-chain-enhancer of activated B cells; particulate matter; polycyclic aromatic hydrocarbons; superoxide dismutase; tumor necrosis factor-alpha; unfolded protein response; versatile aerosol concentrator system
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