Modulation of alpha-crystallin chaperone activity in diabetic rat lens by curcumin.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kumar
P Anil
PA
National Institute of Nutrition, Hyderabad, India.
Suryanarayana
P
P
Reddy
P Yadagiri
PY
Reddy
G Bhanuprakash
GB
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002386:Cataract / Q000378:metabolism* / Q000503:physiopathology; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003474:Curcumin / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004032:Diet; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism*; D051381:Rats; D013050:Spectrometry, Fluorescence; D038201:alpha-Crystallins / Q000378:metabolism*
D000975:Antioxidants; D001786:Blood Glucose; D018832:Molecular Chaperones; D038201:alpha-Crystallins; D003474:Curcumin