Transcriptional responses to intermittent hypoxia.
Transcriptional responses to intermittent hypoxia.
复制标题
DOI：
10.1016/j.resp.2008.07.006
复制
发表时间：
2008-12-10
影响因子：
2.3
通讯作者：
Prabhakar, Nanduri R.
中科院分区：
文献类型：
--
作者：
Nanduri, Jayasri;Yuan, Guoxiang;Kumar, Ganesh K.;Semenza, Gregg L.;Prabhakar, Nanduri R.
关键词：
复发性呼吸暂停的特征是短暂的重复呼吸停止（两次呼吸持续时间或更长），导致动脉血PO2周期性下降或慢性间歇性缺氧（IH）。复发性呼吸暂停患者和暴露于慢性IH的实验动物表现出心肺疾病。本文的目的是强调与慢性IH相关的转录机制的最新信息。对啮齿动物和细胞培养的研究表明，IH激活多种转录因子，包括缺氧诱导因子-1 （HIF-1）、c-fos（即时早期基因）、活化t细胞核因子（NFAT）和核因子kB （NF-kB）。与IH相关的转录激活相关的信号通路与持续缺氧（CH）不同。与相同持续时间和强度的CH相比，IH在激活HIF-1和c-fos方面更有效，并导致HIF-1α和c-fos mRNA的长期积累，这一现象在CH中没有发现。IH诱导的HIF-1、c-fos以及由此产生的激活蛋白1 （AP-1）的转录激活需要活性氧（ROS）介导的信号传导，并涉及HIF-1和ROS之间复杂的前反馈相互作用。Hif-1a+/−小鼠不存在慢性IH引起的心肺反应，缺乏NFAT3c小鼠不存在慢性IH引起的高血压。这些研究表明，慢性IH的心肺反应依赖于各种转录因子之间复杂的相互作用，导致一些下游基因及其蛋白产物的改变。
Recurrent apneas are characterized by transient repetitive cessations of breathing (two breaths duration or longer) resulting in periodic decreases in arterial blood PO2 or chronic intermittent hypoxia (IH). Patients with recurrent apneas and experimental animals exposed to chronic IH exhibit cardio-respiratory morbidities. The purpose of this article is to highlight the current information on the transcriptional mechanisms associated with chronic IH. Studies on rodents and cell cultures have shown that IH activates a variety of transcription factors including the hypoxia-inducible factor-1 (HIF-1), c-fos (immediate early gene), nuclear factor of activated T-Cells (NFAT), and nuclear factor kB (NF-kB). The signaling pathways associated with transcriptional activation associated with IH differ from continuous hypoxia (CH). Compared to same duration and intensity of CH, IH is more potent in activating HIF-1 and c-fos and also results in long-lasting accumulation of HIF-1α and c-fos mRNA, a phenomenon that was not seen with CH. IH-evoked transcriptional activation by HIF-1, c-fos as well as the resulting activator protein-1 (AP-1) requires reactive oxygen species (ROS)-mediated signaling and involves complex feed-forward interactions between HIF-1 and ROS. Chronic IH evoked cardio-respiratory responses are absent in Hif-1a+/− mice, and hypertension elicited by chronic IH is absent in mice lacking NFAT3c. These studies indicate that cardio-respiratory responses to chronic IH depend on complex interactions between various transcription factors resulting in alterations in several down stream genes and their protein products.
登录
查看更多内容
影响因子：
2
作者：
Lam, Siu-Yin;Tipoe, George L.;Fung, Man-Lung
通讯作者：
Fung, Man-Lung
DOI：
10.1046/j.1365-201x.2003.01083.x
发表时间：
2003-03-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Kara, T;Narkiewicz, K;Somers, VK
通讯作者：
Somers, VK
影响因子：
5.5
作者：
Kumar, Ganesh K.;Rai, Vandana;Prabhakar, Nanduri R.
通讯作者：
Prabhakar, Nanduri R.
DOI：
10.1016/j.bbrc.2006.03.015
发表时间：
2006-05-05
影响因子：
3.1
作者：
Greenberg, H;Ye, XB;Liu, SF
通讯作者：
Liu, SF
影响因子：
5.5
作者：
Peng, Ying-Jie;Yuan, Guoxiang;Prabhakar, Nanduri R.
通讯作者：
Prabhakar, Nanduri R.