Kevin Schey
Last active: 3/24/2020

Quantification of thioether-linked glutathione modifications in human lens proteins.

Wang Z, Schey KL
Exp Eye Res. 2018 175: 83-89

PMID: 29879394 · PMCID: PMC6167147 · DOI:10.1016/j.exer.2018.06.002

Dehydroalanine (DHA) and dehydrobutyrine (DHB) intermediates, formed through β-elimination, induce protein irreversible glutathionylation and protein-protein crosslinking in human lens fiber cells. In total, irreversible glutathionylation was detected on 52 sites including cysteine, serine and threonine residues in 18 proteins in human lenses. In this study, the levels of GSH modification on three serine residues and four cysteine residues located in seven different lens proteins isolated from different regions and different aged lenses were quantified. The relative levels of modification (modified/nonmodified) were site-specific and age-related, ranging from less than 0.05% to about 500%. The levels of modification on all of the sites quantified in the lens cortex increased with age and GSH modification also increased from cortex to outer nucleus region suggesting an age-related increase of modification. The levels of modification on sites located in stable regions of the proteins such as Cys117 of βA3, Cys80 of βB1 and Cys27 of γS, continued increasing in inner nucleus, but modification on sites located in regions undergoing degradation with age decreased in the inner nucleus suggesting GSH modified proteins were more susceptible to further modification. Irreversible GSH modification in cataract lenses was typically higher than in age-matched normal lenses, but the difference did not reach statistical significance for a majority of sites, with the exception Cys117 of βA3 crystallin in WSF. Except for S59 of αA and αB crystallins, GSH modification did not induce protein insolubility suggesting a possible role for this modification in protection from protein-protein crosslinking.

Copyright © 2018 Elsevier Ltd. All rights reserved.

MeSH Terms (19)

Adolescent Alanine Aminobutyrates Cataract Cellular Senescence Chromatography, Liquid Crystallins Cysteine Glutathione Humans Lens, Crystalline Middle Aged Protein Processing, Post-Translational Serine Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Sulfides Threonine Tissue Donors Young Adult

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