Abstract
Abstract: :
Purpose: Decline in the chaperone–like function of α–crystallin in diabetic conditions has been reported. In this study, we investigated whether curcumin, a potential antioxidant, can modulate the chaperone–like activity of α–crystallin in diabetic rat lens. Methods: A group of rats received i.p. injection of streptozotocin (STZ; 35 mg/ kg b.w.) to induce hyperglycemia, while another group of rats received 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 by slit lamp biomicroscope. At the end of 8 weeks animals were sacrificed and lenses were collected. αH– and αL–Crystallins from a set of pooled lenses in each group were isolated by gel filtration. Chaperone activity, hydrophobicity and secondary and tertiary structure of αH– and αL–crystallins were assessed. Another set of lenses was used for the estimation of protein carbonyls, lipid peroxidation and reduced glutathione. Results: Progression and maturation of cataract, induced by hyperglycemia, was delayed in a dose dependent manner by curcumin feeding compared to untreated diabetic rats. A decrease in chaperone–like activity that was associated with reduced hydrophobicity and altered secondary and tertiary structure of αH– and αL–crystallins was observed in STZ–treated diabetic rats. Interestingly, αH– and αL–crystallins isolated from curcumin fed diabetic rat lenses had shown improved chaperone–like activity as compared to αH– and αL–crystallins from untreated diabetic rat lens. Feeding of curcumin prevented the alterations in hydrophobicity and structural changes due to STZ–induced hyperglycemia. Altered chaperone activity and structural changes in αH– and αL–crystallins of diabetic cataract rat lens appears to be due to increased oxidative stress as there was a marked increase in protein carbonyl content and lipid peroxidation as well as drastic fall in reduced glutathione levels. Being an antioxidant, curcumin feeding has prevented not only the oxidative stress but also the oxidative stress–induced changes to α–crystallin.<br /Conclusions: Curcumin, a potential dietary antioxidant, modulates the chaperone–like activity of α–crystallin vis–à–vis cataractogenesis due to diabetes in rat lens.
Keywords: chaperones • diabetes • nutritional factors