The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells.
The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells.
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丙烯醛对人支气管上皮细胞中过氧蛋白，硫氧还蛋白和硫氧还蛋白还原酶的影响。
DOI：
10.1016/j.tox.2008.12.013
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发表时间：
2009-03-04
期刊：
影响因子：
4.5
通讯作者：
Myers, Judith M.
中科院分区：
文献类型：
--
作者：
Myers, Charles R.;Myers, Judith M.
吸入是接触丙烯醛的常见形式，丙烯醛是一种有毒的反应性挥发性醛，是一种普遍存在的环境污染物。支气管上皮细胞将直接暴露于吸入的丙烯醛。硫氧还蛋白（Trx）系统是维持细胞巯基氧化还原平衡所必需的，并且对细胞存活至关重要。正常情况下，硫氧还蛋白还原酶（TrxR）使细胞溶质（Trx 1）和线粒体（Trx 2）硫氧还蛋白保持还原状态，硫氧还蛋白使过氧化物酶（Prx）保持还原状态，从而支持其过氧化物酶功能。测定了丙烯醛对人支气管上皮细胞（BEAS-2B）TrxR、Trx和Prx的影响。在5 μM丙烯醛中暴露30分钟后，Trx 1和Trx 2都被氧化，尽管在丙烯醛浓度更低时，Trx 1也受到了显著影响。对Trx 1和Trx 2的影响不能被二硫键还原剂逆转。2.5和5 μM丙烯醛分别抑制TrxR活性60%和>85%。内源性电子供体的TrxR，NADPH，不能恢复其活性，和活性没有恢复在细胞中在4小时的丙烯醛在完全培养基中的自由期。因此，丙烯醛对TrxR和Trx的影响超出了暴露的持续时间。虽然TrxR抑制和Trx 1氧化之间有很强的相关性，但对Trx 1的不可逆影响表明丙烯醛的直接影响，而不是TrxR还原当量的损失。Trx 2直到≥90%的TrxR被抑制才被氧化，但对Trx 2的不可逆作用也表明丙烯醛的直接作用。Prx 1（胞质）和Prx 3（线粒体）只有在> 90%和100%的各自Trx被氧化时才转变为大部分氧化状态。Prx氧化很容易逆转与二硫化物还原剂，这表明Prx氧化导致缺乏从Trx的还原当量，而不是直接与丙烯醛反应。丙烯醛对硫氧还蛋白系统和过氧化物氧还蛋白的影响可能对细胞存活、氧化还原敏感性细胞信号传导和对其他氧化剂损伤的耐受性具有重要影响。
Inhalation is a common form of exposure to acrolein, a toxic reactive volatile aldehyde that is a ubiquitous environmental pollutant. Bronchial epithelial cells would be directly exposed to inhaled acrolein. The thioredoxin (Trx) system is essential for the maintenance of cellular thiol redox balance, and is critical for cell survival. Normally, thioredoxin reductase (TrxR) maintains the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins in the reduced state, and the thioredoxins keep the peroxiredoxins (Prx) reduced, thereby supporting their peroxidase function. The effects of acrolein on TrxR, Trx and Prx in human bronchial epithelial (BEAS-2B) cells were determined. A 30-min exposure to 5 μM acrolein oxidized both Trx1 and Trx2, although significant effects were noted for Trx1 at even lower acrolein concentrations. The effects on Trx1 and Trx2 could not be reversed by treatment with disulfide reductants. TrxR activity was inhibited 60% and >85% by 2.5 and 5 μM acrolein, respectively. The endogenous electron donor for TrxR, NADPH, could not restore its activity, and activity did not recover in cells during a 4-hr acrolein-free period in complete medium. The effects of acrolein on TrxR and Trx therefore extend beyond the duration of exposure. While there was a strong correlation between TrxR inhibition and Trx1 oxidation, the irreversible effects on Trx1 suggest direct effects of acrolein rather than loss of reducing equivalents from TrxR. Trx2 did not become oxidized until ≥90% of TrxR was inhibited, but irreversible effects on Trx2 also suggest direct effects of acrolein. Prx1 (cytosolic) and Prx3 (mitochondrial) shifted to a largely oxidized state only when >90 and 100% of their respective Trxs were oxidized. Prx oxidation was readily reversed with a disulfide reductant, suggesting that Prx oxidation resulted from lack of reducing equivalents from Trx and not direct reaction with acrolein. The effects of acrolein on the thioredoxin system and peroxiredoxins could have important implications for cell survival, redox-sensitive cell signaling, and tolerance to other oxidant insults.
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影响因子：
3.7
作者：
Anestål K;Prast-Nielsen S;Cenas N;Arnér ES
通讯作者：
Arnér ES
影响因子：
4.8
作者：
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DOI：
10.1152/ajplung.1998.274.4.l591
发表时间：
1998-04-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
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作者：
Gurr, JR;Wang, ASS;Jan, KY
通讯作者：
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