title: Formaldehyde impairs transepithelial sodium transport.
abstract: Unsaturated oxidative formaldehyde is a noxious aldehyde in cigarette smoke that causes edematous acute lung injury. However, the mechanistic effects of formaldehyde on lung fluid transport are still poorly understood. We examined how formaldehyde regulates human epithelial sodium channels (ENaC) in H441 and expressed in Xenopus oocytes and exposed mice in vivo. Our results showed that formaldehyde reduced mouse transalveolar fluid clearance in vivo. Formaldehyde caused a dose-dependent inhibition of amiloride-sensitive short-circuit Na+currents in H441 monolayers and of αβγ-ENaC channel activity in oocytes. α-ENaC protein was reduced, whereas phosphorylation of the extracellular regulated protein kinases 1 and 2 (ERK1/2) increased significantly post exposure. Moreover, both α- and γ-ENaC transcripts were down-regulated. Reactive oxygen species (ROS) was elevated significantly by formaldehyde in addition to markedly augmented membrane permeability of oocytes. These data suggest that formaldehyde contributes to edematous acute lung injury by reducing transalveolar Na+transport, through decreased ENaC activity and enhanced membrane depolarization, and by elevating ROS production over long-term exposure.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning, China.
authors.forename: Sihui
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Runzhen
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning, China.
authors.forename: Deyi
authors.initials: D
authors.lastname: Du
authors.affiliation: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning, China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Hong-Long
authors.initials: HL
authors.lastname: Ji
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014981:Xenopus / Q000254:growth & development
chemical_list: D053503:Epithelial Sodium Channels; D005419:Flavonoids; D021122:Protein Subunits; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005557:Formaldehyde; D000584:Amiloride; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one