Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation

Udupa, Padmanabha EG (2008) Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation. The Journal of Biological Chemistry, 283 (13). pp. 8477-8485.

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Analysis of aged and cataract lenses shows the presence of increased amounts of crystallin fragments in the high molecular weight aggregates of water-soluble and water-insoluble fractions. However, the significance of accumulation and interaction of low molecular weight crystallin fragments in aging and cataract development is not clearly understood. In this study, 23 low molecular mass (<3.5-kDa) peptides in the urea-soluble fractions of young, aged, and aged cataract human lenses were identified by mass spectroscopy. Two peptides, B-(1–18) (MDIAIHHPWIRRPFFPFH) and �A3/A1-(59–74) (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, �S-(167–178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact �-, �-, and �-crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of �B-(1–18) and �A3/A1-(59–74) peptides increased the scattering of light by�- and�-crystallin and alcohol dehydrogenase. The ability of �-crystallin subunits to function as molecular chaperones was significantly reduced by interaction with �B-(1–18) and �A3/ A1-(59–74) peptides, whereas�S peptide had no effect on chaperone- like activity of �-crystallin. The �A3/A1-(59–74 peptide caused a 5.64-fold increase in�B-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in�B-(1–18) and �A3/A1-(59–74) peptides abolished their ability toinduce crystallin aggregation and light scattering. Our study suggests that interaction of crystallin-derived peptides with intact crystallins could be a key event in age-related protein aggregation in lens and cataractogenesis.

Item Type: Article
Subjects: Medicine > KMC Manipal > Biochemistry
Depositing User: KMC Manipal
Date Deposited: 05 Aug 2015 04:19
Last Modified: 05 Aug 2015 04:19

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