Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments.
Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments.
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DOI：
10.1016/j.freeradbiomed.2012.02.042
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发表时间：
2012-05-01
影响因子：
7.4
通讯作者：
Forman, Henry Jay
中科院分区：
文献类型：
--
作者：
Zhang, Hongqiao;Liu, Honglei;Davies, Kelvin J. A.;Sioutas, Constantinos;Finch, Caleb E.;Morgan, Todd E.;Forman, Henry Jay
许多异生物质解毒（第二阶段）酶诱导亚致死剂量的环境毒物。然而，这些自适应机制还没有被研究，在响应车辆来源的空气中的纳米尺寸的颗粒物（nPM）。由于衰老与对环境毒物的敏感性增加有关，我们还研究了中年小鼠中Nrf 2调节的II期基因的表达及其慢性nPM的诱导作用。在城市洛杉矶收集来自车辆交通的nPM，并将其重新雾化，以供C57 BL/6 J雄性小鼠（3和18月龄）在10周内暴露150小时。通过RT-PCR和/或蛋白质印迹法测定脑（小脑）、肝脏和肺II相酶的表达：谷氨酸半胱氨酸连接酶（催化GCLC和修饰剂GCLM亚基）、NAD（P）H：醌氧化还原酶1（NQO 1）、血红素加氧酶1（HO-1）和相关转录因子：NF-E2相关因子2（Nrf 2）、c-Myc、Bach 1。慢性nPM暴露诱导GCLC，GCLM，HO-1，NQO 1的mRNA和蛋白在小脑，肝脏和肺的年轻小鼠相似。中年小鼠的基础水平升高，但表现出受损的进一步诱导nPM。同样，Nrf 2随着年龄的增长而增加，并且在年轻时而不是老年时被nPM诱导。c-Myc显示出相同的年龄和诱导特征，而Bach 1的年龄增加进一步由nPM诱导。慢性暴露于纳米颗粒诱导Nrf 2调节的解毒酶在大脑（小脑），肝脏和肺的年轻成年小鼠表明nPM的全身影响。相比之下，中年小鼠除了Bach 1外，对高于其升高的基础水平没有反应。衰老小鼠中II相酶诱导的缺乏可能是老年人对空气污染的脆弱性的模型。
Many xenobiotic detoxifying (phase II) enzymes are induced by sublethal doses of environmental toxicants. However, these adaptive mechanisms have not been studied in response to vehicular-derived airborne nano-sized particulate matter (nPM). Because aging is associated with increased susceptibility to environmental toxicants, we also examined the expression of Nrf2-regulated phase II genes in middle-aged mice and their inducibility by chronic nPM. The nPM from vehicular traffic was collected in urban Los Angeles and re-aerosolized for exposure of C57BL/6J male mice (3 and 18 months old) for 150 hours over 10 weeks. Brain (cerebellum), liver, and lung were assayed by RT-PCR and/or western blots for the expression of phase II enzymes: glutamate cysteine ligase (catalytic GCLC, and modifier GCLM subunits), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), and relevant transcription factors: NF-E2 related factor 2 (Nrf2), c-Myc, Bach1. Chronic nPM exposure induced GCLC, GCLM, HO-1, NQO1 mRNA and protein similarly in cerebellum, liver, and lung of young mice. Middle-aged mice had elevated basal levels, but showed impaired further induction by nPM. Similarly, Nrf2 increased with age and was induced by nPM in young but not old. c-Myc showed the same age- and induction- profile while the age-increase in Bach1 was further induced by nPM. Chronic exposure to nanoparticles induced Nrf2-regulated detoxifying enzymes in brain (cerebellum), liver, and lung of young adult mice indicating a systemic impact of nPM. In contrast, middle-aged mice did not respond above their elevated basal levels except for Bach1. The lack of induction of phase II enzymes in aging mice may be a model for the vulnerability of elderly to air pollution.
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影响因子：
10
作者：
Araujo JA;Nel AE
通讯作者：
Nel AE
DOI：
10.1093/gerona/51a.3.b183
发表时间：
1996-05-01
影响因子：
5.1
作者：
Finch, CE;Pike, MC
通讯作者：
Pike, MC
NRF2：氧化应激中的INRF2（KEAP1）信号传导。
影响因子：
7.4
作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
通讯作者：
Jaiswal, Anil K.
影响因子：
15.9
作者：
Block, Michelle L.;Calderon-Garciduenas, Lilian
通讯作者：
Calderon-Garciduenas, Lilian
影响因子：
4.8
作者：
Alam, J;Stewart, D;Cook, JL
通讯作者：
Cook, JL