Modulation of α-crystallin chaperone activity in diabetic rat lens by curcumin

α-Crystallin, a small heat shock protein (sHSP), constitutes the major portion of eye lens cytoplasm and its concentration in the lens can reach up to 50% of the total protein. Like other sHSP, α-crystallin displays chaperone-like activity in suppressing the aggregation of various proteins and in preventing inactivation of enzymes due to heat and other stress conditions [1-6]. Hence, in addition to providing refractive properties to the lens for focusing the image, it is believed that the molecular chaperone function of α-crystallin is essential in preventing the light scattering due to aggregation of other proteins and thus in the maintenance of lens transparency and thereby prevention of cataract [1-3]. α-Crystallin, especially αB-crystallin, is also present in various non-lenticular tissues, albeit at very low levels [7]. Both in vitro and in vivo studies established the importance of α-crystallin in the biology of the lens and in the physiology of other tissues [2,7-10]. Being a long lived protein with slow turnover, αcrystallin is known to undergo extensive posttranslational modifications (PTMs) including oxidation, mixed disulfide formation, truncation, and glycation during aging [1,11-13]. Moreover, the chaperone activity of α-crystallin is shown to be influenced/compromised by most of these modifications [1,14-17]. As a corollary to this, it has also been demonstrated that α-crystallin from aged lenses has decreased chaperone activity [18,19]. Chronic hyperglycemia is a major determinant in the development of secondary complications of diabetes, including diabetic cataract. Studies indicate that hyperglycemia and the duration of diabetes increase the risk of development of cataract [20-22]. In view of the widespread prevalence of diabetes in developing countries [23], diabetic cataract may pose a major problem in the management of blindness. Hence, chaperone function of α-crystallin under hyperglycemic conditions is of great concern with respect to lens transparency. Indeed α-crystallin from diabetic rat and human lenses has shown a substantial loss in its chaperone function [24,25]. Furthermore, α-crystallin chaperone activity was also found to be impaired in galactosemic rat lenses [26]. These studies imply that impaired chaperone function of α-crystallin could be involved in the formation of diabetic cataract. Therefore, it is essential to investigate the ways and means by which we can maintain and/or prevent the loss of chaperone potential of α-crystallin under diabetic conditions. We reported earlier that curcumin, the active principle of turmeric and a dietary antioxidant, at very low levels in the diet, delayed cataract in rats induced by either galactose feeding or streptozotocin (STZ) treatment ©2005 Molecular Vision