Cytoprotection of prostaglandin under oxidative stress

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炎症介质的产生。我们前期的研究表明，PG具有释放氧化应激的作用，如视网膜缺血/再灌注和视网膜光氧化。采用大鼠视网膜光损伤模型，观察光照后环氧合酶-1 （Cox-1）、Cox-2、PGE_2、PGD_2、PGF_<2->的变化。24小时后PGD_2的表达增加了光感受器外节段。光照后Cox-2、PGE_2、PGF_<2->均无明显变化。我们证实，在光照条件下，8-羟基脱氧鸟苷（8-OhdG），一种主要的DNA碱基修饰产物，在外核层增加。我们考察了n -乙酰半胱氨酸（NAC）在该项目中的作用。NAC是外源硫醇类抗氧化剂之一。细胞或组织中硫醇含量的增加与氧化应激耐受性的增加有关。NAC抑制了光诱导的光感受器细胞DNA损伤的减弱，提示NAC恢复了光诱导的光感受器细胞损伤。我们观察到脂质过氧化降低和硫氧还蛋白上调，表明NAC减轻了氧化应激。NAC通过抑制氧化应激来减弱光诱导的光感受器细胞损伤，而控制细胞内氧化还原状态可能是一种有用的治疗策略。

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.