NADPH DEPENDENT REDUCTASES IN CATARACT FORMATION

萘白内障已被广泛用作人类老年性白内障的模型 白内障，因为氧化是这种白内障的基本机制 阵最近的兴趣，这种白内障已重新由 有证据表明，一些醛糖还原酶（AR）抑制剂可以防止 萘喂养大鼠白内障的形成。 虽然AR是醛酮还原酶家族的成员， 利用NADPH还原多种芳香族和脂肪族醛 和酮转化为相应的醇，这种酶还具有 脱氢酶活性和利用萘-1，2-二氢二醇， 萘的主要代谢物。因为二氢二醇 脱氢酶不存在于大鼠透镜中， 萘-1，2-二氢二醇主要来源于AR。的分析 LCMS和GCMS都证实了来自 大鼠透镜AR为1，2-萘醌。大鼠 用萘-1，2-二氢二醇孵育的透镜产生黑暗 微黄色的蛋白质-萘醌加合物，也是由 体外孵育透镜蛋白和萘-1，2-二氢二醇。两 含乙内酰脲和非乙内酰脲AR抑制剂可阻止这种蛋白 改性 证据清楚地表明，AR在以下代谢中是重要的： 萘在大鼠透镜中，并最终在形成中起关键作用 白内障因为人类AR具有与人类AR相同的 活动，AR可能在一些毒性白内障中发挥作用。

Naphthalene cataract has been widely used as a model for human senile cataract because oxidation is the basic mechanism of this cataract formation. Recent interest in this cataract has been renewed by the evidence that some of the aldose reductase (AR) inhibitors prevent the formation of cataract in naphthalene-fed rats. Although AR is a member of a family of aldo-keto reductases, which utilizes NADPH to reduce a wide range of aromatic and aliphatic aldehydes and ketones to their corresponding alcohols, this enzyme also possesses the dehydrogenase activity and utilizes naphthalene-1,2-dihydrodiol, one of the major metabolites of naphthalene. Because dihydrodiol dehydrogenase is not present in rat lens, the activity to naphthalene-1,2-dihydrodiol is mainly derived from AR. The analysis by both LCMS and GCMS confirms that the metabolite from naphthalene-1,2-dihydrodiol by rat lens AR is 1,2-naphthoquinone. Rat lens incubated with naphthalene-1,2-dihydrodiol generates the dark yellowish protein-naphthoquinone adducts that are also created by the incubation of lens protein and naphthalene-1,2-dihydrodiol in vitro. Both hydantoin-containing and nonhydantoin AR inhibitors prevent this protein modification. The evidence clearly indicates that AR is important in the metabolism of naphthalene in rat lens and eventually plays a key role in the formation of cataract. Because human AR has the same dihydrodiol dehydrogenase activity, AR may play a role in some toxic cataracts.