Cytoprotection of prostaglandin under oxidative stress

氧化应激下前列腺素的细胞保护

基本信息

批准号：
11671739
负责人：
OHIRA Akihiro
金额：
$ 2.3万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Prostaglandin (PG) has various biological functions including breakdown of blood-retinal barrier and production of mediators in inflammations. Our previous study indicated that PG has release from oxidative stress, such as retinal ischemia/reperfusion and retinal photooxidation. We used the retinal light damage in rats, and observed the changes of cyclooxygenase-1 (Cox-1), Cox-2, PGE_2, PGD_2, and PGF_<2-> after light exposure. PGD_2 expression increased the photoreceptor outer segments after 24 hours. No changes were observed Cox-2, PGE_2, and PGF_<2-> after light exposure. We confirmed the increase of 8-hydroxy-deoxyguanosine (8-OhdG), one of the major DNA base-modified products, in the outer nuclear layaer during periods of light challenges. We examined the effect of N-acetylcysteine (NAC) in this project. NAC is one of exogenous thiol antioxidants. Increased level of thiols in cells or tissues associate with increased tolerance to oxidative stresses. NAC precluded the light induced diminishment of DNA damage of photoreceptor cells, suggesting that NAC restored light induced damage of photoreceptor cells. We observed decreased lipid peroxidation and thioredoxin upregulation, indicating that NAC attenuated oxidative stress. NAC administration attenuates the light induced photoreceptor cell damage via the suppression of oxidative stress, and manipulation of intracellular redox state may represent a useful therapeutic strategy.

前列腺素（PG）具有各种生物学功能，包括血液 - 视网膜屏障的分解和炎症中介体的产生。我们先前的研究表明，PG从氧化应激中释放出来，例如视网膜缺血/再灌注和视网膜光氧化。我们使用了大鼠的视网膜光损伤，并观察了光暴露后环氧酶-1（COX-1），COX-1，PGE_2，PGD_2，PGD_2，PGD_2，PGE_2，PGD_2和PGF_ <2->的变化。 24小时后，PGD_2表达增加了光感受器的外部段。光暴露后未观察到COX-2，PGE_2和PGF_ <2->。在光挑战期间，我们证实了主要的DNA碱基修饰产物之一，证实了8-羟基脱氧鸟苷（8-OHDG），这是主要的DNA碱基修饰产物之一。我们检查了N-乙酰半胱氨酸（NAC）在该项目中的影响。 NAC是外源性硫醇抗氧化剂之一。与氧化应激的耐受性相关的细胞或组织中硫醇水平的增加。 NAC排除了光感受器细胞DNA损伤的降低，这表明NAC恢复了光感受器细胞的损伤。我们观察到脂质过氧化和硫氧还蛋白上调的降低，表明NAC减弱了氧化应激。 NAC给药可通过抑制氧化应激来减轻光感受器细胞损伤，而对细胞内氧化还原态的操纵可能代表了一种有用的治疗策略。