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

Puttur Santhoshkumar, Padmanabha Udupa, Raju Murugesan, K. Krishna Sharma

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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, αB-(1-18) (MDIAIHHPWIRRPFFPFH) and βA3/A1-(59-74) (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, γS-(167-178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact α-,β-, and γ-crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of αB-(1-18) and βA3/A1-(59-74) peptides increased the scattering of light by β- and γ-crystallin and alcohol dehydrogenase. The ability of α-crystallin subunits to function as molecular chaperones was significantly reduced by interaction with αB-(1-18) and βA3/A1-(59-74) peptides, whereas γS peptide had no effect on chaperone-like activity of α-crystallin. The βA3/A1-(59-74 peptide caused a 5.64-fold increase in αB-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in αB-(1-18) and βA3/A1-(59-74) peptides abolished their ability to induce 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.

Original languageEnglish
Pages (from-to)8477-8485
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number13
DOIs
Publication statusPublished - 28-03-2008

Fingerprint

Crystallins
Cataract
Lenses
Aging of materials
Molecular Weight
Molecular weight
Peptides
Agglomeration
Alcohol Dehydrogenase
Light
Molecular Chaperones
Water
Molecular mass
Light scattering
Urea
Mass Spectrometry
Proteins
Spectroscopy
Scattering

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Santhoshkumar, Puttur ; Udupa, Padmanabha ; Murugesan, Raju ; Sharma, K. Krishna. / Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 13. pp. 8477-8485.
@article{a6f2e3c9ded04541aaf993084cf268f2,
title = "Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation",
abstract = "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, αB-(1-18) (MDIAIHHPWIRRPFFPFH) and βA3/A1-(59-74) (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, γS-(167-178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact α-,β-, and γ-crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of αB-(1-18) and βA3/A1-(59-74) peptides increased the scattering of light by β- and γ-crystallin and alcohol dehydrogenase. The ability of α-crystallin subunits to function as molecular chaperones was significantly reduced by interaction with αB-(1-18) and βA3/A1-(59-74) peptides, whereas γS peptide had no effect on chaperone-like activity of α-crystallin. The βA3/A1-(59-74 peptide caused a 5.64-fold increase in αB-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in αB-(1-18) and βA3/A1-(59-74) peptides abolished their ability to induce 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.",
author = "Puttur Santhoshkumar and Padmanabha Udupa and Raju Murugesan and Sharma, {K. Krishna}",
year = "2008",
month = "3",
day = "28",
doi = "10.1074/jbc.M705876200",
language = "English",
volume = "283",
pages = "8477--8485",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation. / Santhoshkumar, Puttur; Udupa, Padmanabha; Murugesan, Raju; Sharma, K. Krishna.

In: Journal of Biological Chemistry, Vol. 283, No. 13, 28.03.2008, p. 8477-8485.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation

AU - Santhoshkumar, Puttur

AU - Udupa, Padmanabha

AU - Murugesan, Raju

AU - Sharma, K. Krishna

PY - 2008/3/28

Y1 - 2008/3/28

N2 - 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, αB-(1-18) (MDIAIHHPWIRRPFFPFH) and βA3/A1-(59-74) (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, γS-(167-178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact α-,β-, and γ-crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of αB-(1-18) and βA3/A1-(59-74) peptides increased the scattering of light by β- and γ-crystallin and alcohol dehydrogenase. The ability of α-crystallin subunits to function as molecular chaperones was significantly reduced by interaction with αB-(1-18) and βA3/A1-(59-74) peptides, whereas γS peptide had no effect on chaperone-like activity of α-crystallin. The βA3/A1-(59-74 peptide caused a 5.64-fold increase in αB-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in αB-(1-18) and βA3/A1-(59-74) peptides abolished their ability to induce 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.

AB - 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, αB-(1-18) (MDIAIHHPWIRRPFFPFH) and βA3/A1-(59-74) (SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, γS-(167-178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact α-,β-, and γ-crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of αB-(1-18) and βA3/A1-(59-74) peptides increased the scattering of light by β- and γ-crystallin and alcohol dehydrogenase. The ability of α-crystallin subunits to function as molecular chaperones was significantly reduced by interaction with αB-(1-18) and βA3/A1-(59-74) peptides, whereas γS peptide had no effect on chaperone-like activity of α-crystallin. The βA3/A1-(59-74 peptide caused a 5.64-fold increase in αB-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in αB-(1-18) and βA3/A1-(59-74) peptides abolished their ability to induce 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.

UR - http://www.scopus.com/inward/record.url?scp=43749091530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43749091530&partnerID=8YFLogxK

U2 - 10.1074/jbc.M705876200

DO - 10.1074/jbc.M705876200

M3 - Article

VL - 283

SP - 8477

EP - 8485

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -