title: Zinc ions as effectors of environmental oxidative lung injury.
abstract: The redox-inert transition metal Zn is a micronutrient that plays essential roles in protein structure, catalysis, and regulation of function. Inhalational exposure to ZnO or to soluble Zn salts in occupational and environmental settings leads to adverse health effects, the severity of which appears dependent on the flux of Zn(2+) presented to the airway and alveolar cells. The cellular toxicity of exogenous Zn(2+) exposure is characterized by cellular responses that include mitochondrial dysfunction, elevated production of reactive oxygen species, and loss of signaling quiescence leading to cell death and increased expression of adaptive and inflammatory genes. Central to the molecular effects of Zn(2+) are its interactions with cysteinyl thiols, which alters their functionality by modulating their reactivity and participation in redox reactions. Ongoing studies aimed at elucidating the molecular toxicology of Zn(2+) in the lung are contributing valuable information about its role in redox biology and cellular homeostasis in normal and pathophysiology.
authors.affiliation: School of Public Health XinXiang Medical University XinXiang, China 453003; Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
authors.affiliation: Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Bromberg
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. EPA, Chapel Hill, NC 27514, USA. Electronic address: Samet.James@EPA.GOV.
authors.forename: James M
authors.initials: JM
authors.lastname: Samet
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000009:adverse effects*; D006801:Humans; D055370:Lung Injury / Q000139:chemically induced*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000009:adverse effects; D015032:Zinc / Q000009:adverse effects*
chemical_list: D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D015032:Zinc
keywords: AP-1; ASL; Air pollution; CCO; CF; COX-2; Csk; DMEM; DMT1; DUOX; Dulbeccos’ minimal essential medium; EGFR; ERK; GDP; GSH; GSK-3β; GSSG; GTP; HO-1; IKK; IL-1; IkB; IkB kinase; JNK; Keap1; Kelch-like ECH-associated protein 1; Lung injury; MAPK; MAPKK; MAPKKK; MT; MTF-1; Metals; Myc; N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1-2-ethanediamine; NADH; NADPH; NADPH oxidoreductase; NFkB; NOX; NRAMP; Nrf2; Oxidant stress; PDK1; PI3K; PIP2; PIP3; PKB; PKC; PM; PP; PTEN; PTP; RNS; ROS; Reactive oxygen species; SHP-1; SLC; Ser; Serine; TNF; TPEN; TRPA1; Zinc; Zinc transporter (SLC 30); Zinc transporter (SLC 39); Zip; ZnT; adaptor protein 1; airway surface liquid; c-jun N-terminal kinase; c-src kinase; cyclooxygenase 2; cystic fibrosis; cytochrome c oxidase; divalent metal ion transporter 1; dual oxidase; epidermal growth factor receptor; extracellular-signal-regulated kinases; glutathione; glycogen synthase kinase 3 beta; guanosine diphosphate; guanosine triphosphate; heme oxygenase 1; inhibitor of kappa B; interleukin 1 (6, 8, etc.); mPTP; metal-responsive transcription factor 1; metallothionein; mitochondrial permeability transition pore; mitogen activated protein kinase; mitogen activated protein kinase kinase; mitogen activated protein kinase kinase kinase; myelocytomatosis gene; natural resistance-associated macrophage protein; nicotinamide adenine dinucleotide phosphate; nicotinamide dinucleotide; nuclear factor (erythroid-derived 2)-like 2; nuclear factor kappa B; oxidized glutathione; particulate matter; phosphatase and tensin homolog; phosphatidylinositol-3,4,5-trisphosphate; phosphatidylinositol-3-kinase; phosphatidylinositol-4,5-bisphosphate; pleckstrin homology domain kinase; protein kinase B; protein kinase C; protein phosphatase; protein tyrosine phosphatase; reactive nitrogen species; reactive oxygen species; redox sensing green fluorescent protein; roGFP; solute-linked carrier; src-homology region 2 domain-containing phosphatase 1; transient receptor potential with ankyrin repeats; tumor necrosis factor