title: Copper Deficiency in the Lungs of TNF-α Transgenic Mice.
abstract: Tumor necrosis factor (TNF)-α is a well-known pro-inflammatory cytokine. Increased expression of Tnf-α is a feature of inflammatory lung diseases, such as asthma, emphysema, fibrosis, and smoking-induced chronic obstructive pulmonary disease (COPD). Using a mouse line with lung-specific Tnf-α overexpression (SPC-TNF-α) to mimic TNF-α-associated lung diseases, we investigated the role of chronic inflammation in the homeostasis of lung trace elements. We performed a quantitative survey of micronutrients and biometals, including copper (Cu), zinc (Zn), and selenium (Se), in the transgenic mice tissues. We also examined the expression of Cu-dependent proteins in the inflammatory lung tissue to determine whether they were affected by the severe Cu deficiency, including cuproenzymes, Cu transporters, and Cu chaperones. We found consistent lung-specific reduction of the metal Cu, with a mean decrease of 70%; however, Zn and Se were unaffected in all other tissues. RT-PCR showed that two Cu enzymes associated with lung pathology were downregulated: amine oxidase, Cu containing 3 (Aoc3) and lysyl oxidase (Lox). Two factors, vascular endothelial growth factor (Vegf) and focal adhesion kinase (Fak), related with Cu deficiency treatment, showed decreased expression in the transgenic inflammatory lung. We concluded that Cu deficiency occurs following chronic TNF-α-induced lung inflammation and this likely plays an essential role in the inflammation-induced lung damage. These results suggest the restoration of lung Cu status as a potential strategy in both treatment and prevention of chronic lung inflammation and related disorders.
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: McDermott
authors.affiliation: Department of Pathology, Creighton University School of Medicine Omaha, NE, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Cody
authors.initials: C
authors.lastname: Corbin
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Xuan
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Jae
authors.initials: J
authors.lastname: Kim
authors.affiliation: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center Columbus, OH, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Biological Sciences, Oakland University Rochester, MI, USA.
authors.forename: Zijuan
authors.initials: Z
authors.lastname: Liu
keywords: COPD; biometals; inflammation; micronutrients; oxidative stress