High mobility group A1 protein mediates human nitric oxide synthase 2 gene expression
- 作者：Rina Takamiya ; Rebecca M. Baron ; Shaw-Fang Yet ; Matthew D. Layne ; Mark A. Perrella
- 关键词：Nitric oxide synthase 2 ; High mobility group A1 ; Pro-inflammatory cytokine
- 刊名：FEBS Letters
- 出版年：2008
- 期刊代码：70_00145793
- 类别：bio
- 出版时间：5 March 2008
- 卷：582
- 期：5
- 页码：810-814
- 文件大小：134 K
摘要
Nitric oxide synthase (NOS)2, an inducible enzyme that produces NO during inflammation, is transcriptionally regulated. Our goal was to determine whether high mobility group (HMG)A1 contributes to human (h)NOS2 gene regulation. Using a small molecule inhibitor of HMGA1 binding to DNA, or a dominant-negative form of HMGA1, we blunted the induction of hNOS2 by pro-inflammatory stimuli. Binding of HMGA1 in the region −3506 to −3375 of the hNOS2 promoter, a region not previously known to be involved in hNOS2 regulation, contributed to the induction of hNOS2 promoter in conjunction with upstream enhancer regions. We demonstrate a previously unknown role for HMGA1 in the regulation of hNOS2.