Kumar P Anil, Suryanarayana P, Reddy P Yadagiri, Reddy G Bhanuprakash
National Institute of Nutrition, Hyderabad, India.
Mol Vis. 2005 Jul 26;11:561-8.
A decline in the chaperone-like activity of eye lens alpha-crystallin in diabetic conditions has been reported. In this study, we investigated whether curcumin, a dietary antioxidant, can manipulate the chaperone-like activity of alpha-crystallin in diabetic rat lens.
A group of rats received ip injection of streptozotocin (STZ; 35 mg/kg body weight in buffer) to induce hyperglycemia, while another group of rats received only buffer as vehicle and served as control. STZ-treated rats were assigned to 3 groups and fed either no curcumin or 0.002% or 0.01% curcumin, respectively. Cataract progression due to hyperglycemia was monitored with a slit lamp biomicroscope. At the end of 8 weeks animals were sacrificed and lenses were collected. alphaH- and alphaL-crystallins from a set of pooled lenses in each group were isolated by gel filtration. Chaperone activity, hydrophobicity, and secondary and tertiary structure of alphaH- and alphaL-crystallins were assessed by light scattering/spectroscopic methods.
A decrease in chaperone-like activity of alphaH- and alphaL-crystallins was observed in STZ-treated diabetic rats. The declined chaperone-like activity due to hyperglycemia was associated with reduced hydrophobicity and altered secondary and tertiary structure of alphaH- and alphaL-crystallins. Interestingly, alphaH- and alphaL-crystallins isolated from curcumin fed diabetic rat lenses had shown improved chaperone-like activity as compared to alphaH- and alphaL-crystallins from untreated diabetic rat lens. Feeding of curcumin prevented the alterations in hydrophobicity and structural changes due to STZ-induced hyperglycemia. Modulation of functional and structural properties by curcumin was found to be greater with the alphaL-crystallin than alphaH-crystallin. Loss of chaperone activity of alpha-crystallin, particularly alphaL-crystallin, in diabetic rat lens could be attributed at least partly to increased oxidative stress. Being an antioxidant, curcumin feeding has prevented the loss of alpha-crystallin chaperone activity and delayed the progression and maturation of diabetic cataract.
We demonstrate that curcumin, at the levels close to dietary consumption, prevented the loss of chaperone-like activity of alpha-crystallin vis-a-vis cataractogenesis due to diabetes in rat lens.
据报道，在糖尿病状态下，眼晶状体α-晶状体蛋白的伴侣样活性会下降。在本研究中，我们调查了姜黄素（一种膳食抗氧化剂）是否能调控糖尿病大鼠晶状体中α-晶状体蛋白的伴侣样活性。
一组大鼠腹腔注射链脲佐菌素（STZ；缓冲液中35 mg/kg体重）以诱导高血糖，而另一组大鼠仅注射缓冲液作为对照。将经STZ处理的大鼠分为3组，分别喂食不含姜黄素、0.002%或0.01%姜黄素的饲料。用裂隙灯生物显微镜监测高血糖导致的白内障进展情况。8周结束时处死动物并收集晶状体。通过凝胶过滤从每组的一组合并晶状体中分离出αH-和αL-晶状体蛋白。通过光散射/光谱方法评估αH-和αL-晶状体蛋白的伴侣活性、疏水性以及二级和三级结构。
在经STZ处理的糖尿病大鼠中，观察到αH-和αL-晶状体蛋白的伴侣样活性下降。高血糖导致的伴侣样活性下降与αH-和αL-晶状体蛋白的疏水性降低以及二级和三级结构改变有关。有趣的是，与未处理的糖尿病大鼠晶状体中的αH-和αL-晶状体蛋白相比，从喂食姜黄素的糖尿病大鼠晶状体中分离出的αH-和αL-晶状体蛋白显示出改善的伴侣样活性。喂食姜黄素可防止因STZ诱导的高血糖导致的疏水性改变和结构变化。发现姜黄素对αL-晶状体蛋白的功能和结构特性的调节作用比对αH-晶状体蛋白的调节作用更大。糖尿病大鼠晶状体中α-晶状体蛋白，尤其是αL-晶状体蛋白的伴侣活性丧失至少部分可归因于氧化应激增加。作为一种抗氧化剂，喂食姜黄素可防止α-晶状体蛋白伴侣活性的丧失，并延缓糖尿病性白内障的进展和成熟。
我们证明，在接近膳食摄入量的水平下，姜黄素可防止大鼠晶状体中α-晶状体蛋白因糖尿病导致的白内障形成而丧失伴侣样活性。
