NADPH DEPENDENT REDUCTASES IN CATARACT FORMATION

萘性白内障已被广泛用作人类老年性白内障的模型 因为氧化是这种白内障的基本机制 队形。最近对这种白内障的兴趣重新引起了 有证据表明，一些醛糖还原酶(AR)抑制剂可以防止 喂萘大鼠白内障的形成。 虽然AR是醛酮还原酶家族的成员，该家族 利用NADPH降低多种芳香族和脂肪族醛 和酮对应的醇，这种酶还拥有 脱氢酶活性和利用萘-1，2-二氢二酚，一 萘的主要代谢物。因为二氢二醇 脱氢酶在大鼠晶状体中不存在，活性为 萘-1，2-二氢二酚主要来源于AR。这一分析由 LC MS和GCMS都证实了来自 大鼠晶状体AR测定的1，2-萘二酚为1，2-萘二酚。大鼠 与萘-1，2-二氢二酚孵育的晶状体产生黑暗 黄色蛋白质-萘醌加合物，也是由 晶体蛋白与1，2-二氢萘二酚体外孵育。两者都有 含海因和不含海因的AR抑制剂可阻止该蛋白 修改。 证据清楚地表明，AR在人体的新陈代谢中起着重要作用。 在大鼠晶状体中并最终在形成过程中起关键作用 白内障的症状。因为人类AR具有相同的二氢二醇脱氢酶 在某些中毒性白内障中，AR可能起一定作用。

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.