Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner.
Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner.
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DOI：
10.1038/srep34424
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发表时间：
2016-09-29
影响因子：
4.6
通讯作者：
Hirota K
中科院分区：
文献类型：
--
作者：
Daijo H;Hoshino Y;Kai S;Suzuki K;Nishi K;Matsuo Y;Harada H;Hirota K
香烟烟雾（CS）是导致大量致命和衰弱性疾病的主要因素。然而，CS在肺部疾病中的作用的确切分子机制在很大程度上是未知的。为了阐明这些病理生理过程，我们研究了CS提取物（CSE）和CS对转录因子缺氧诱导因子1（HIF-1）的体外和体内影响。非缺氧条件下CSE诱导人肺上皮样细胞中HIF-1α蛋白的浓度和时间依赖性积累HIF-1上调的基因，包括血管内皮生长因子和调节发育和DNA损伤反应1，这两者都参与吸烟诱导的肺气肿的变化，增加了CSE治疗在体外和体内非缺氧条件下。进一步的研究表明，在暴露于CSE的细胞中产生活性氧，并且是CSE介导的HIF-1α蛋白诱导所需的，磷酸肌醇3-激酶和丝裂原活化蛋白激酶途径的激活也是如此。总之，我们证明了CSE和CS分别在体外和体内诱导HIF-1活化。有证据表明，HIF-1在CS诱导的基因表达中起重要作用，这与肺细胞应激和小气道重塑密切相关。
Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions. Genes upregulated by HIF-1, including vascular endothelial growth factor and regulated in development and DNA damage response 1, both of which are involved in smoking-induced emphysematous changes, were increased by CSE treatment under non-hypoxic conditions in vitro and in vivo. Further investigation revealed that reactive oxygen species were generated in cells exposed to CSE and were required for CSE-mediated induction of HIF-1α protein, as was activation of phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. In conclusion, we demonstrated that CSE and CS induced HIF-1 activation in vitro and in vivo, respectively. The evidence warrants further investigation to indicate that HIF-1 plays an important role in CS-induced gene expression, which is deeply involved in pulmonary cellular stress and small airway remodelling.
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影响因子：
5.8
作者：
Demedts, Ingel K.;Demoor, Tine;Bracke, Ken R.;Joos, Guy F.;Brusselle, Guy G.
通讯作者：
Brusselle, Guy G.
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
DOI：
10.1152/ajplung.00466.2001
发表时间：
2003-06-01
影响因子：
4.9
作者：
Carnevali, S;Petruzzelli, S;Giuntini, C
通讯作者：
Giuntini, C
影响因子：
4.8
作者：
Kasuno, K;Takabuchi, S;Hirota, K
通讯作者：
Hirota, K
影响因子：
56.9
作者：
Bruick, RK;McKnight, SL
通讯作者：
McKnight, SL