Major Shifts in the Spatio-Temporal Distribution of Lung Antioxidant Enzymes during Influenza Pneumonia
Major Shifts in the Spatio-Temporal Distribution of Lung Antioxidant Enzymes during Influenza Pneumonia
复制标题
流感肺炎期间肺抗氧化酶时空分布的重大变化
作者：
Yoshiyuki Yamada;G. Limmon;Dahai Zheng;Na Li;Liang Li;Lu Yin;V. Chow;Jianzhu Chen;B. Engelward
随着我们呼吸的空气不断受到挑战，肺组织承受着最高水平的氧张力，因此需要强大的抗氧化防御。此外，受伤或感染后，肺组织面临炎症诱导的活性氧和活性氮（ROS/RNS）的额外挑战。对于正常条件下或感染引起的炎症期间肺抗氧化酶的特性或分布知之甚少。使用流感小鼠模型（H1N1 流感病毒 A/PR/8/34 [PR8]）并结合生物信息学，我们鉴定了七种肺部丰富的抗氧化酶：谷胱甘肽过氧化物酶 3 (Gpx3)、超氧化物歧化酶 3 (Sod3)、转铁蛋白 (Tf)、过氧氧化还原蛋白 6 (Prdx6)、谷胱甘肽 S-转移酶 kappa 1 (Gstk1)、过氧化氢酶 (Cat) 和谷胱甘肽过氧化物酶 8 (Gpx8)。有趣的是，尽管炎症期间需要抗氧化剂，但流感导致两种关键抗氧化剂的消耗：Cat 和 Prdx6。由于 Cat 在 Clara 细胞中高表达，病毒诱导的 Clara 细胞损失导致了 Cat 的耗竭。由于 Clara 细胞损失，Prdx6 也会减少，但肺泡中的 Prdx6 水平同时增加，导致总体上 Prdx6 仅略有减少。类似地，Gpx3 从细支气管和血管下方的基底膜转移到肺泡，从而保持平衡的表达。总的来说，这些研究确定了关键的肺部抗氧化剂，并揭示了它们在特定细胞类型中的分布。此外，结果表明，流感消耗了关键的抗氧化剂，并且在某些情况下，表达同时增加，与补偿性表达一致。鉴于已知氧化应激是流感感染期间的关键危险因素，了解肺部的抗氧化成分以及抗氧化剂的时空分布，有助于我们了解流感引起的发病率和死亡率的潜在机制。
With the incessant challenge of exposure to the air we breathe, lung tissue suffers the highest levels of oxygen tension and thus requires robust antioxidant defenses. Furthermore, following injury or infection, lung tissue faces the additional challenge of inflammation-induced reactive oxygen and nitrogen species (ROS/RNS). Little is known about the identity or distribution of lung antioxidant enzymes under normal conditions or during infection-induced inflammation. Using a mouse model of influenza (H1N1 influenza virus A/PR/8/34 [PR8]) in combination with bioinformatics, we identified seven lung-abundant antioxidant enzymes: Glutathione peroxidase 3 (Gpx3), Superoxide dismutase 3 (Sod3), Transferrin (Tf), peroxyredoxin6 (Prdx6), glutathione S-transferase kappa 1 (Gstk1), Catalase (Cat), and Glutathione peroxidase 8 (Gpx8). Interestingly, despite the demand for antioxidants during inflammation, influenza caused depletion in two key antioxidants: Cat and Prdx6. As Cat is highly expressed in Clara cells, virus-induced Clara cell loss contributes to the depletion in Cat. Prdx6 is also reduced due to Clara cell loss, however there is a coincident increase in Prdx6 levels in the alveoli, resulting in only a subtle reduction of Prdx6 overall. Analogously, Gpx3 shifts from the basement membranes underlying the bronchioles and blood vessels to the alveoli, thus maintaining balanced expression. Taken together, these studies identify key lung antioxidants and reveal their distribution among specific cell types. Furthermore, results show that influenza depletes key antioxidants, and that in some cases there is coincident increased expression, consistent with compensatory expression. Given that oxidative stress is known to be a key risk factor during influenza infection, knowledge about the antioxidant repertoire of lungs, and the spatio-temporal distribution of antioxidants, contributes to our understanding of the underlying mechanisms of influenza-induced morbidity and mortality.
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DOI：
10.1152/ajpgi.00064.2011
发表时间：
2011-07-01
影响因子：
4.5
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Yin, Dengping
DOI：
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Jacoby, DB
克拉拉细胞：支气管上皮的祖细胞。
DOI：
10.1016/j.biocel.2009.09.002
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2010-01
影响因子：
4
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Reynolds, Susan D.;Malkinson, Alvin M.
通讯作者：
Malkinson, Alvin M.
DOI：
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影响因子：
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Olson, Gary E.;Whitin, John C.;Burk, Raymond F.
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DOI：
10.1165/ajrcmb.17.4.2826
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影响因子：
6.4
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Folz, RJ;Guan, JZ;Crapo, JD
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Crapo, JD