MECHANISMS THAT REGULATE THE ENZYMES THAT METABOLIZE CIS UNSATURATED FATTY ACIDS

调节顺式不饱和脂肪酸代谢酶的机制

• 批准号: 2574401
• 负责人: T ELING
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2574401
• 关键词: enzyme activity; enzyme mechanism; fatty acid metabolism; gene expression; human tissue; laboratory rat; ligands; lipopolysaccharides; messenger RNA; molecular cloning; nitric oxide; oxygenases; peroxidases; phorbols; prostaglandins; tissue /cell culture; unsaturated fatty acids

Our studies with PGHS-1 indicate that a Tyr radical is formed by the peroxidase activity of PGHS-1. Our data suggest that the Tyr radical is not the reactive intermediate that initiates arachidonic acid oxygenation. Recently we have shown that NO reacts with the tyrosyl radical converting the radical to a new radical characterized by ESR analysis. Reaction of the tyrosyl radical with NO does not alter the formation of prostaglandins and support the conclusion that the tyrosyl radical is not responsible for the removal of the 13-pro-R-hydrogen that initiates the cyclooxygenase reaction. These findings are being prepared for publication. Nitric oxide(NO) is reported to enhance prostaglandin formation by direct enhancement of PGHS activity. We found that NO is a substrate for the peroxidase but does not enhance the cyclooxygenase activity. Also, NO does not stimulate the expression of PGHS or alter LPS dependent PGHS-2 expression. We have also cloned rat PGHS-1 and -2 and studied their expression by rat tracheal cells (EGV-6). We observed an aberrantly sliced PGHS-1 mRNA in addition to the complete mRNA. Furthermore, we observed in these cells that TPA up-regulated PGHS-1 which in most cells is not upregulated by ligands but constitutively regulated. We have shown that EGF regulates the formation of 13-HODE in Syrian hamster embryo (SHE) cells.

我们对PGHS-1的研究表明，Tyr自由基是由 PGHS-1的过氧化物酶活性。我们的数据表明Tyr自由基是 而不是引发花生四烯酸的活性中间体 氧合 最近，我们已经表明，NO与酪氨酰反应， 自由基将自由基转化为ESR表征的新自由基 分析.酪氨酰基自由基与NO的反应不改变 并支持酪氨酰 自由基不负责去除13-pro-R-氢， 引发环氧合酶反应。 这些调查结果正在编写中 出版。 据报道，一氧化氮（NO）可增强前列腺素 通过直接增强PGHS活性形成。 我们发现NO是 过氧化物酶的底物，但不增强环氧合酶 活动 此外，NO不刺激PGHS的表达或改变PGHS的表达。 LPS依赖性PGHS-2表达。 我们还克隆了大鼠PGHS-1和-2 用大鼠气管上皮细胞（EGV-6）研究其表达。 我们观察到 除了完整的mRNA外，还存在异常切割的PGHS-1 mRNA。 此外，我们在这些细胞中观察到TPA上调PGHS-1， 其在大多数细胞中不被配体上调，而是组成性地 监管. 我们已经证明，EGF调节13-HODE的形成， 叙利亚仓鼠胚胎（SHE）细胞。