Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells
Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells
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DOI：
10.1016/j.bbrc.2005.01.089
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Hänze, J
中科院分区：
文献类型：
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作者：
Goyal, P;Weissmann, N;Hänze, J
NAD（P）H氧化酶（Nox）产生活性氧（ROS），其在宿主防御和细胞信号传导中起作用。在蛋白质和mRNA水平上分析Nox 4的表达时，我们鉴定了四种新的Nox 4剪接变体Nox 4B、Nox 4C、Nox 4D和Nox 4E，它们在人肺A549细胞系和肺组织中表达。一种Nox4同种型缺乏第一个NAD（P）H结合位点（Nox4B），而另一种缺乏所有FADH和NAD（P）H结合位点（Nox4C）。过表达NoxB或Nox4C的细胞表现出ROS水平的降低。因此，这些同种型对ROS产生具有显性负性特征。另外两种剪接变体（Nox4D）、Nox4E）缺乏跨膜结构域，表明它们是非膜相关的同种型。Nox4D包含所有FADH和NAD（P）H结合结构域，并显示与Nox4原型相同的ROS产生速率。Taker，我们一起认为，Nox 4作为几种亚型存在，可能在ROS相关的细胞信号传导中具有不同的功能。（C）2005年爱思唯尔公司All rights reserved.
NAD(P)H oxidases (Nox) generate reactive oxygen species (ROS) that function in host defense and cellular signaling. While analyzing he expression of Nox4 at the protein and the rnRNA levels, we identified four novel Nox4 splice-variants Nox4B, Nox4C, Nox4D, and Nox4E, which are expressed in human lung A549 cell line and lung tissues. One Nox4 isoform lacks the first NAD(P)H binding site (Nox4B) while another lacks all FADH and NAD(P)H binding sites (Nox4C). Cells over-expressing NoxB or Nox4C exhibited a decrease in ROS levels. Thus, these isoforms have dominant negative characteristics for ROS generation. Two other splice-variants (Nox4D), Nox4E) lack the transmembrane domains, suggesting these as non-membrane associated isoforms. Nox4D contains all FADH and NAD(P)H binding domains and shows the same rate of ROS generation as Nox4 prototype. Taker, together, we suggest that Nox4 exists as several isoforms that may have different functions in ROS-related cell signaling. (C)2005 Elsevier Inc. All rights reserved.