Regulation of Heme Oxygenase Expression by Cyclopentenone Prostaglandins
Regulation of Heme Oxygenase Expression by Cyclopentenone Prostaglandins
复制标题
环戊烯酮前列腺素对血红素加氧酶表达的调节
DOI：
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发表时间：
2003
影响因子：
3.2
通讯作者：
S. Doré
中科院分区：
文献类型：
--
作者：
H. Zhuang;Sokhon Pin;Xiaoling Li;S. Doré
前列腺素 (PG) 源自环加氧酶（COX-1 和 COX-2）对膜花生四烯酸的降解。前列腺素在神经系统中的作用是多种的，并且已被认为在神经退行性疾病中发挥重要作用。据报道，一些 PG 具有毒性，有趣的是，据报道，环戊烯酮 PG 在低浓度下具有细胞保护作用，并且可能在神经元可塑性中发挥重要作用。它们已被证明可以预防氧化应激损伤；然而，这些 PG 提供的细胞保护机制仍不清楚。据推测，在急性和慢性神经退行性疾病（例如脑缺血和阿尔茨海默病）中导致神经元细胞死亡的级联反应是由自由基损伤介导的。我们测试了这样的假设：环戊酮的神经保护作用可能部分是由血红素加氧酶 1 (HO-1) 的诱导引起的。我们和其他人之前曾报道过，HO 总活性的调节很可能对中风和阿尔茨海默氏病具有直接的生理影响。 H2O 充当抗氧化酶，将血红素降解为铁、一氧化碳和胆绿素，胆绿素迅速转化为胆红素。使用小鼠原代神经元培养物，我们证明 J 系列的 PG 以剂量依赖性方式（0、0.5、5、10、20 和 50 μg/ml）诱导 HO-1，并且 PGJ2 和 dPGJ2 比 PGA2、dPGA2、PGD2 和 PGE2 更有效。没有观察到 HO-2 和肌动蛋白表达的显着影响。至于在大鼠中发现的HO-3表达，其蛋白推导序列与HO-2高度同源，在HO-2−/−小鼠中未观察到HO-3蛋白的表达，表明HO-3蛋白在小鼠脑中不会存在。我们提出 PGJ2 的一些保护作用可以通过血红素降解及其代谢物的有益作用来介导。基于环戊烯酮结构的新模拟物的设计可以作为神经保护剂非常有用，并可以在中风和阿尔茨海默病的动物模型中进行测试。
Prostaglandins (PGs) originate from the degradation of membranar arachidonic acid by cyclooxygenases (COX-1 and COX-2). The prostaglandin actions in the nervous system are multiple and have been suggested to play a significant role in neurodegenerative disorders. Some PGs have been reported to be toxic and, interestingly, the cyclopentenone PGs have been reported to be cytoprotective at low concentration and could play a significant role in neuronal plasticity. They have been shown to be protective against oxidative stress injury; however, the cellular mechanisms of protection afforded by these PGs are still unclear. It is postulated that the cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer’s disease, would be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of cyclopentanone could be caused partially by an induction of heme oxygenase 1 (HO-1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer’s disease. HO acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin that is rapidly converted into bilirubin. Using mouse primary neuronal cultures, we demonstrated that PGs of the J series induce HO-1 in a dose-dependent manner (0, 0.5, 5, 10, 20, and 50 μg/ml) and that PGJ2 and dPGJ2 were more potent than PGA2, dPGA2, PGD2, and PGE2. No significant effects were observed for HO-2 and actin expression. In regard to HO-3 expression found in rat, with its protein deducted sequence highly homologous to HO-2, no detection was observed in HO-2−/− mice, suggesting that HO-3 protein would not be present in mouse brain. We are proposing that several of the protective effects of PGJ2 could be mediated through beneficial actions of heme degradation and its metabolites. The design of new mimetics based on the cyclopentenone structure could be very useful as neuroprotective agents and be tested in animal models of stroke and Alzheimer’s disease.
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DOI：
10.1111/j.1432-1033.1997.00725.x
发表时间：
1997-07-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
McCoubrey, WK;Huang, TJ;Maines, MD
通讯作者：
Maines, MD
影响因子：
56.9
作者：
VERMA, A;HIRSCH, DJ;SNYDER, SH
通讯作者：
SNYDER, SH
原卟啉调节 AtT-20 垂体细胞中的电压门控 Ca 电流。
影响因子：
2.5
作者：
Linden,DJ;Narasimhan,K;Gurfel,D
通讯作者：
Gurfel,D
DOI：
10.1073/pnas.94.20.10919
发表时间：
1997-09-30
影响因子：
11.1
作者：
Poss, KD;Tonegawa, S
通讯作者：
Tonegawa, S
血红蛋白和铁引起的大脑氧化应激：胆汁色素、锰和 S-亚硝基谷胱甘肽的保护。
影响因子：
3.3
作者：
VanBergen,P;Rauhala,P;Spooner,CM;Chiueh,CC
通讯作者：
Chiueh,CC