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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) 具有多种生物学功能，包括破坏血视网膜屏障和产生炎症介质。我们之前的研究表明，PG可以缓解视网膜缺血/再灌注和视网膜光氧化等氧化应激。我们利用大鼠视网膜光损伤，观察光照射后环氧合酶-1（Cox-1）、Cox-2、PGE_2、PGD_2、PGF_<2->的变化。 24小时后，PGD_2表达增加了光感受器外节。光照后未观察到Cox-2、PGE_2和PGF_ 2- 的变化。我们证实了在光照挑战期间外核层中主要 DNA 碱基修饰产物之一 8-羟基脱氧鸟苷 (8-OhdG) 的增加。我们研究了 N-乙酰半胱氨酸 (NAC) 在此项目中的作用。 NAC是外源性硫醇抗氧化剂之一。细胞或组织中硫醇水平的增加与氧化应激耐受性的增加相关。 NAC 排除了光诱导的感光细胞 DNA 损伤的减弱，表明 NAC 恢复了光诱导的感光细胞损伤。我们观察到脂质过氧化减少和硫氧还蛋白上调，表明 NAC 减轻了氧化应激。 NAC 给药通过抑制氧化应激来减轻光诱导的感光细胞损伤，并且操纵细胞内氧化还原状态可能代表一种有用的治疗策略。