Copper Deficiency in the Lungs of TNF-α Transgenic Mice
| Autor: | Liu Liu, Jae Kim, Zijuan Liu, Jian Shen, Joseph McDermott, Cody Corbin, Xiangrong Geng, Stephanie Xuan, Li Zuo |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology medicine.medical_treatment Lysyl oxidase Inflammation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fibrosis Physiology (medical) Internal medicine medicine COPD oxidative stress Original Research Lung Chemistry respiratory system medicine.disease respiratory tract diseases 3. Good health Vascular endothelial growth factor biometals 030104 developmental biology Endocrinology Cytokine medicine.anatomical_structure inflammation micronutrients 030220 oncology & carcinogenesis Immunology Tumor necrosis factor alpha medicine.symptom Copper deficiency |
| Zdroj: | Frontiers in Physiology |
| ISSN: | 1664-042X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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