Human alveolar epithelial cell injury induced by cigarette smoke.
Human alveolar epithelial cell injury induced by cigarette smoke.
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DOI：
10.1371/journal.pone.0026059
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mason RJ
中科院分区：
文献类型：
--
作者：
Kosmider B;Messier EM;Chu HW;Mason RJ
香烟烟雾（CS）是一种高度复杂的混合物，其许多成分是已知的致癌物、诱变剂和其他有毒物质。CS诱导氧化应激和细胞死亡，这种细胞毒性在几种肺部疾病的发病机制中起着关键作用。我们研究了香烟烟雾提取物（CSE）在人肺泡上皮I型样（ATI样）细胞中的作用。这些是分离的II型细胞，其在体外向I型细胞表型分化，并且已经丢失了许多II型细胞标志物并表达I型细胞标志物。ATI样细胞比肺泡II型细胞对CSE更敏感，肺泡II型细胞在体外保持其分化表型。采用吖啶橙子-溴化乙锭或Hoechst 33342-碘化丙啶双染法和TUNEL法检测CSE处理后线粒体膜电位的改变、凋亡和坏死。检测caspase 3和caspase 7活性及脂质过氧化反应。CSE可诱导Nrf 2核转位，增加Nrf 2、HO-1、Hsp 70和Fra 1的表达。此外，我们发现Nrf 2敲低使ATI样细胞对CSE敏感，Nrf 2过表达提供了对CSE诱导的细胞死亡的保护。我们还观察到两种抗氧化剂化合物N-乙酰半胱氨酸和trolox保护ATI样细胞免受CSE损伤。我们的研究表明，Nrf 2活化是人肺泡上皮细胞防御CSE诱导的毒性和氧化应激的主要因素。因此，调节Nrf 2的抗氧化剂有望恢复抗氧化和解毒酶，预防CS相关的肺损伤，并可能减轻肺气肿的发展。
Cigarette smoke (CS) is a highly complex mixture and many of its components are known carcinogens, mutagens, and other toxic substances. CS induces oxidative stress and cell death, and this cell toxicity plays a key role in the pathogenesis of several pulmonary diseases. We studied the effect of cigarette smoke extract (CSE) in human alveolar epithelial type I-like (ATI-like) cells. These are isolated type II cells that are differentiating toward the type I cell phenotype in vitro and have lost many type II cell markers and express type I cell markers. ATI-like cells were more sensitive to CSE than alveolar type II cells, which maintained their differentiated phenotype in vitro. We observed disruption of mitochondrial membrane potential, apoptosis and necrosis that were detected by double staining with acridine orange and ethidium bromide or Hoechst 33342 and propidium iodide and TUNEL assay after treatment with CSE. We also detected caspase 3 and caspase 7 activities and lipid peroxidation. CSE induced nuclear translocation of Nrf2 and increased expression of Nrf2, HO-1, Hsp70 and Fra1. Moreover, we found that Nrf2 knockdown sensitized ATI-like cells to CSE and Nrf2 overexpression provided protection against CSE-induced cell death. We also observed that two antioxidant compounds N-acetylcysteine and trolox protected ATI-like cells against injury by CSE. Our study indicates that Nrf2 activation is a major factor in cellular defense of the human alveolar epithelium against CSE-induced toxicity and oxidative stress. Therefore, antioxidant agents that modulate Nrf2 would be expected to restore antioxidant and detoxifying enzymes and to prevent CS-related lung injury and perhaps lessen the development of emphysema.
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DOI：
10.1152/ajplung.00148.2009
发表时间：
2009-11-01
影响因子：
4.9
作者：
Ferguson, Heather E.;Thatcher, Thomas H.;Sime, Patricia J.
通讯作者：
Sime, Patricia J.
DOI：
10.1152/ajplung.2001.280.6.l1189
发表时间：
2001-06-01
影响因子：
4.9
作者：
Ishii, T;Matsuse, T;Ouchi, Y
通讯作者：
Ouchi, Y
影响因子：
3.8
作者：
Cho, Hye-Youn;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.
DOI：
10.1158/1055-9965.epi-09-0965
发表时间：
2009-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Johnson MD;Schilz J;Djordjevic MV;Rice JR;Shields PG
通讯作者：
Shields PG
DOI：
10.1152/ajplung.90215.2008
发表时间：
2008-10-01
影响因子：
4.9
作者：
Baglole, Carolyn J.;Sime, Patricia J.;Phipps, Richard P.
通讯作者：
Phipps, Richard P.