5-S-GAD, a novel radical scavenging compound, prevents lens opacity development
5-S-GAD, a novel radical scavenging compound, prevents lens opacity development
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DOI：
10.1016/j.freeradbiomed.2008.11.010
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发表时间：
2009-02-15
影响因子：
7.4
通讯作者：
Natori, Shunji
中科院分区：
文献类型：
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作者：
Akiyama, Nobuko;Umeda, Izumi O.;Natori, Shunji
研究了从昆虫中分离的新型儿茶酚衍生物5-S-GAD抑制自由基和预防白内障进展的能力。5-S-GAD清除DPPH和超氧阴离子（O（2）（中点-）），抑制脂质过氧化。它还显著抑制鸡胚中糖皮质激素诱导的透镜混浊的发生。5-S-GAD的这些作用强于N-乙酰肌肽和TEMPOL，据报道，N-乙酰肌肽和TEMPOL是预防白内障进展的有效自由基清除剂。5-S-GAD能明显延缓联胺诱导的大鼠白内障的成熟。每日滴注5-S-GAD可延缓半乳糖喂养大鼠透镜混浊的发生。晶状体的生化分析显示，20-kDa蛋白质（可能由α-晶状体蛋白组成）对氧化应激最敏感，这导致这些蛋白质侧链的羰基化。5-S-GAD以密切依赖的方式显著抑制联酰胺或半乳糖诱导的α-晶体蛋白碳酰化。我们的研究结果表明，5-S-GAD防止急性透镜混浊在这些短期的实验模型，可能是部分凭借其抗氧化性能，和5-S-GAD预计有长期的药物作用。(C)2008年爱思唯尔公司All rights reserved.
The ability of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD)-a novel catechol derivative isolated from an insect as an antibacterial substance-to scavenge free radicals and prevent cataract progression was examined. 5-S-GAD scavenged 1,1-diphenylpicrylhydrazyl (DPPH) and superoxide anions (O(2)(center dot-)), and inhibited lipid peroxidation. it also significantly inhibited the onset of glucocorticoid-induced lens opacification in chick embryos. These effects of 5-S-GAD were stronger than those of N-acetylcarnosine and TEMPOL, which are reported to be effective radical scavengers in the prevention of cataract progression. 5-S-GAD clearly delayed the maturation of cataracts induced by diamide in cultured lenses of rats. Daily instillation of 5-S-GAD retarded the development of lens opacity in galactose-fed rats. Biochemical analysis of the lenses revealed that 20-kDa proteins, presumably consisting of alpha-crystallin, were the Most Susceptible to oxidative stress, which leads to the carbonylation of the side chains of these proteins. alpha-Crystallin carborylation induced by diamide or galactose was notably inhibited by 5-S-GAD in a close-dependent manner. Our results show that 5-S-GAD prevents acute lens opacification in these short-term experimental models, possibly in part by virtue of its antioxidative property, and 5-S-GAD is expected to have long-term pharmaceutical effects. (C) 2008 Elsevier Inc. All rights reserved.