Faculty of Pharmacy, Keio University, Tokyo, 105-8512 Japan.
Faculty of Pharmacy, Kindai University, Osaka, 577-8502, Japan.
Biomed Pharmacother. 2017 Nov;95:137-143. doi: 10.1016/j.biopha.2017.08.055. Epub 2017 Sep 12.
To prevent lens opacification and cataract formation, the lens contains α-crystallin, which has been shown to function as a molecular chaperone that maintains the correct folding of other proteins. Oxidative stress is known to be an important factor in the initiation and progression of a cataract. So far, several antioxidant compounds have been reported to prevent cataracts in vivo and in vitro. This stress also triggers α-crystallin modifications and alters its chaperone activity. However, few studies have examined the relationship between the consumption of antioxidant compounds and lens chaperone activity. To elucidate the effect of antioxidants on lens chaperone activity, antioxidants were administered to a selenite-induced cataract model of rats. The chaperone activity in lens water-soluble fraction was measured using aldehyde dehydrogenase. All antioxidant treatment groups, except decaffeinated coffee treatment, had less severe central opacities and lower stage cataracts than control groups. The chaperone activity was weaker in lens of selenite cataract rats, but antioxidant compounds and coffee treatment can prevent the chaperone activity decreasing, but not decaffeinated coffee. These results suggested that the treatment with antioxidant compounds could prevent cataract formation by the maintenance of the chaperone activity in water-soluble lens proteins. Thus, this study describes the development of an anticataract drug target for lens chaperone activity.
为了防止晶状体混浊和白内障形成,晶状体中含有α-晶体蛋白,它已被证明具有分子伴侣的功能,可以维持其他蛋白质的正确折叠。氧化应激被认为是白内障发生和发展的一个重要因素。到目前为止,已经有几种抗氧化化合物被报道可以在体内和体外预防白内障。这种应激还会引发α-晶体蛋白的修饰,并改变其伴侣活性。然而,很少有研究检查抗氧化化合物的消耗与晶状体伴侣活性之间的关系。为了阐明抗氧化剂对晶状体伴侣活性的影响,用亚硒酸钠诱导的白内障大鼠模型给予抗氧化剂。使用醛脱氢酶测量晶状体水溶性部分的伴侣活性。除了去咖啡因咖啡处理组外,所有抗氧化处理组的中央混浊程度都比对照组轻,白内障分期也较低。硒白内障大鼠晶状体中的伴侣活性较弱,但抗氧化化合物和咖啡处理可以防止伴侣活性下降,但去咖啡因咖啡不能。这些结果表明,抗氧化剂的治疗可以通过维持水溶性晶状体蛋白中的伴侣活性来预防白内障的形成。因此,本研究描述了一种针对晶状体伴侣活性的白内障药物治疗靶点的开发。