Expression regulation of phospholipid hydroperoxide glutathione peroxidase isoforms. Transcriptional and post-transcriptional processes

磷脂氢过氧化物谷胱甘肽过氧化物酶亚型的表达调节。

• 批准号: 5241220
• 负责人: Professor Dr. Hartmut Kühn
• 金额: --
• 依托单位: Institut für Biochemie (CCM)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5241220?language=en
• 关键词: Expression; regulation; phospholipid; hydroperoxide; glutathione

12/15-Lipoxygenases (12/15-LOX) and phospholipid hydroperoxide glutathione peroxidase (PH-GPx) are counterplayers in the metabolism of complex lipid hydroperoxides. Among LOXs, 12/15-LOXs are unique with respect to their capability of oxygenating ester lipids and PH-GPx is the only glutathione peroxidase capable of reducing hydroperoxy ester lipids. PH-GPx was identified as endogenous regulator of cellular LOX pathways and recently we found that both enzymes are inversely regulated by cytokines. In this project we intend to investigate the mechanism of the functional interplay of both enzymes on transcriptional, translational and pos-translational levels. For this purpose the following questions will be investigated: 1. Is overexpression of functional 12/15-LOX sufficient to down-regulate PH-GPx expression and does vice versa 12/15-LOX knockout up-regulate PH-GPx expression? 2. Which part of the 5'-flanking region of the murine PH-GPx gene contains the promoter (functional promoter studies) and what potential binding sites for transcription factors identified in the 5'-flanking region are functional? 3. Do interleukins-4 (IL-4) and -13 (IL-13) induce the expression of nuclear proteins capable of binding to the promoter of 12/15-LOX and PH-GPx genes and are these potential transcription factor involved in the inverse regulation of both enzymes?

12/15-脂氧合酶（12/15-LOX）和磷脂氢过氧化物谷胱甘肽过氧化物酶（PH-GPx）是复合脂质氢过氧化物代谢中的对应物。在LOX中，12/15-LOX在其氧化酯脂质的能力方面是独特的，并且PH-GPx是唯一能够还原氢过氧酯脂质的谷胱甘肽过氧化物酶。PH-GPx被鉴定为细胞LOX途径的内源性调节剂，并且最近我们发现这两种酶都受到细胞因子的反向调节。在这个项目中，我们打算研究这两种酶在转录，翻译和翻译后水平上的功能相互作用的机制。为此，将研究以下问题：1。功能性12/15-LOX过表达是否足以下调PH-GPx表达，反之亦然，12/15-LOX敲除是否上调PH-GPx表达？2.鼠PH-GPx基因的5 '侧翼区的哪一部分包含启动子（功能性启动子研究），以及在5'侧翼区中鉴定的转录因子的哪些潜在结合位点是功能性的？3.白细胞介素-4（IL-4）和白细胞介素-13（IL-13）是否诱导能够与12/15-LOX和PH-GPx基因的启动子结合的核蛋白的表达，这些潜在的转录因子是否参与这两种酶的反向调节？