title: Transcriptional biomarkers and mechanisms of copper-induced olfactory injury in zebrafish.
abstract: Metals such as copper disrupt olfactory function in fish. Unfortunately, little is understood of the molecular consequences of copper olfactory impairment, thus hindering the development of relevant diagnostic tools of olfactory injury. To address this critical data gap, we analyzed gene expression within olfactory tissues of adult zebrafish exposed to CuCl2 (6, 16, 40 ppb) for 24 h. Transcriptional markers of copper impairment within the entire olfactory system were identified and specific genes of interest (e.g., S100a, parvalbumin 8, olfactory marker protein, and calbindin 2-like protein) were confirmed with quantitative real-time PCR. In addition, we performed gene set analysis (GSA) using both a priori and custom pathways of gene sets specifically targeting the olfactory signal transduction (OST) pathway. These analyses revealed down-regulated gene sets related to calcium channels and ion transport, g-proteins, and olfactory receptors. Collectively, these data demonstrate that copper causes a depression of transcription of key genes within the OST pathway and elsewhere within olfactory tissues, likely resulting in an olfactory system less responsive to odorants. Further, these data provide a mechanistic explanation in support of earlier studies of functional olfactory impairment in fish following copper exposure.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Tilton
authors.forename: Susan C
authors.initials: SC
authors.lastname: Tilton
authors.forename: Theo K
authors.initials: TK
authors.lastname: Bammler
authors.forename: Richard
authors.initials: R
authors.lastname: Beyer
authors.forename: Frederico
authors.initials: F
authors.lastname: Farin
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Stapleton
authors.forename: Evan P
authors.initials: EP
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016000:Cluster Analysis; D003300:Copper / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D000857:Olfaction Disorders / Q000139:chemically induced* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D015027:Zebrafish / Q000235:genetics*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D003300:Copper