Lung injury after ozone exposure is iron dependent
Lung injury after ozone exposure is iron dependent
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DOI：
10.1152/ajplung.00534.2005
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发表时间：
2007-01-01
影响因子：
4.9
通讯作者：
Garrick, Michael D.
中科院分区：
文献类型：
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作者：
Ghio, Andrew J.;Turi, Jennifer L.;Garrick, Michael D.
我们测试的假设，臭氧（O-3）暴露后的氧化应激和生物效应是依赖于铁稳态的变化。O-3暴露后，健康志愿者表现出增加灌洗浓度的铁，转铁蛋白，乳铁蛋白和铁蛋白。在正常大鼠中，O-3暴露后铁代谢的改变是立即的，并在炎症流入之前。为了测试这种破坏在肺损伤后的铁稳态的参与O-3吸入，我们暴露贝尔格莱德大鼠，这是功能缺陷的二价金属转运蛋白1（DMT 1）作为一种手段，铁的吸收，和控制O-3。铁稳态被破坏到更大的程度和损伤的程度是更大的贝尔格莱德大鼠比对照组大鼠。非血红素铁和铁蛋白浓度较高，在人支气管上皮细胞（HBE）细胞暴露于O-3比HBE细胞暴露于过滤空气。O-3暴露后，HBE细胞的醛生成和IL-8释放也升高。将DMT 1构建体表达升高的人胚肾（HEK 293）细胞暴露于过滤空气和O-3。随着暴露于O-3，升高的DMT 1表达减少了氧化应激（即，醛生成）和IL-8释放。我们的结论是，铁参与关键的氧化应激和O3暴露后的生物效应。
We tested the hypothesis that oxidative stress and biological effect after ozone (O-3) exposure are dependent on changes in iron homeostasis. After O-3 exposure, healthy volunteers demonstrated increased lavage concentrations of iron, transferrin, lactoferrin, and ferritin. In normal rats, alterations of iron metabolism after O-3 exposure were immediate and preceded the inflammatory influx. To test for participation of this disruption in iron homeostasis in lung injury following O-3 inhalation, we exposed Belgrade rats, which are functionally deficient in divalent metal transporter 1 (DMT1) as a means of iron uptake, and controls to O-3. Iron homeostasis was disrupted to a greater extent and the extent of injury was greater in Belgrade rats than in control rats. Nonheme iron and ferritin concentrations were higher in human bronchial epithelial (HBE) cells exposed to O-3 than in HBE cells exposed to filtered air. Aldehyde generation and IL-8 release by the HBE cells was also elevated following O-3 exposure. Human embryonic kidney (HEK 293) cells with elevated expression of a DMT1 construct were exposed to filtered air and O-3. With exposure to O-3, elevated DMT1 expression diminished oxidative stress (i.e., aldehyde generation) and IL-8 release. We conclude that iron participates critically in the oxidative stress and biological effects after O3 exposure.