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αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins

PURPOSE: To identify and characterize properties of αA- and αB-crystallins’ low molecular weight peptides (molecular weight [Mr] < 5 kDa) that were present in a 62-year-old human nuclear cataract, but not in normal 62-year-old human lenses. METHODS: Low molecular weight peptides (< 5 kDa) were...

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Autores principales: Srivastava, Om, Wilson, Landon, Barnes, Stephen, Srivastava, Kiran, Joseph, Roy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744240/
https://www.ncbi.nlm.nih.gov/pubmed/36540064
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author Srivastava, Om
Wilson, Landon
Barnes, Stephen
Srivastava, Kiran
Joseph, Roy
author_facet Srivastava, Om
Wilson, Landon
Barnes, Stephen
Srivastava, Kiran
Joseph, Roy
author_sort Srivastava, Om
collection PubMed
description PURPOSE: To identify and characterize properties of αA- and αB-crystallins’ low molecular weight peptides (molecular weight [Mr] < 5 kDa) that were present in a 62-year-old human nuclear cataract, but not in normal 62-year-old human lenses. METHODS: Low molecular weight peptides (< 5 kDa) were isolated with a trichloroacetic acid (TCA) solubilization method from water-soluble (WS) and water-insoluble (WI) proteins of nuclear cataractous lenses of a 62-year-old donor and normal human lenses from an age-matched donor. Five commercially synthesized peptides (found only in cataractous lenses and not in normal lenses) were used to determine their chaperone and antichaperone activity and aggregation properties. RESULTS: Mass spectrometric analysis showed 28 peptides of αA-crystallin and 38 peptides of αB-crystallin were present in the cataractous lenses but not in the normal lenses. Two αA peptides (named αAP1 and αAP2; both derived from the αA N-terminal domain (NTD) region) and three αB peptides (named αBP3, αBP4, and αBP5, derived from the αB NTD-, core domain (CD), and C-terminal extension (CTE) regions, respectively) were commercially synthesized. αAP1 inhibited the chaperone activity of αA- and αB-crystallins, but the other four peptides (αAP2, αBP3, αBP4, and αBP5) exhibited mixed effects on chaperone activity. Upon incubation with human WS proteins and peptides in vitro, the αBP4 peptide showed higher aggregation properties relative to the αAP1 peptide. During in vivo experiments, the cell-penetrating polyarginine-labeled αAP1 and αBP4 peptides showed 57% and 85% aggregates, respectively, around the nuclei of cultured human lens epithelial cells compared to only 35% by a scrambled peptide. CONCLUSIONS: The antichaperone activity of the αAP1 peptide and the aggregation property of the αBP4 peptide with lens proteins could play a potential role during the development of lens opacity.
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spelling pubmed-97442402022-12-19 αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins Srivastava, Om Wilson, Landon Barnes, Stephen Srivastava, Kiran Joseph, Roy Mol Vis Research Article PURPOSE: To identify and characterize properties of αA- and αB-crystallins’ low molecular weight peptides (molecular weight [Mr] < 5 kDa) that were present in a 62-year-old human nuclear cataract, but not in normal 62-year-old human lenses. METHODS: Low molecular weight peptides (< 5 kDa) were isolated with a trichloroacetic acid (TCA) solubilization method from water-soluble (WS) and water-insoluble (WI) proteins of nuclear cataractous lenses of a 62-year-old donor and normal human lenses from an age-matched donor. Five commercially synthesized peptides (found only in cataractous lenses and not in normal lenses) were used to determine their chaperone and antichaperone activity and aggregation properties. RESULTS: Mass spectrometric analysis showed 28 peptides of αA-crystallin and 38 peptides of αB-crystallin were present in the cataractous lenses but not in the normal lenses. Two αA peptides (named αAP1 and αAP2; both derived from the αA N-terminal domain (NTD) region) and three αB peptides (named αBP3, αBP4, and αBP5, derived from the αB NTD-, core domain (CD), and C-terminal extension (CTE) regions, respectively) were commercially synthesized. αAP1 inhibited the chaperone activity of αA- and αB-crystallins, but the other four peptides (αAP2, αBP3, αBP4, and αBP5) exhibited mixed effects on chaperone activity. Upon incubation with human WS proteins and peptides in vitro, the αBP4 peptide showed higher aggregation properties relative to the αAP1 peptide. During in vivo experiments, the cell-penetrating polyarginine-labeled αAP1 and αBP4 peptides showed 57% and 85% aggregates, respectively, around the nuclei of cultured human lens epithelial cells compared to only 35% by a scrambled peptide. CONCLUSIONS: The antichaperone activity of the αAP1 peptide and the aggregation property of the αBP4 peptide with lens proteins could play a potential role during the development of lens opacity. Molecular Vision 2022-08-06 /pmc/articles/PMC9744240/ /pubmed/36540064 Text en Copyright © 2022 Molecular Vision. https://creativecommons.org/licenses/by-nc-nd/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Srivastava, Om
Wilson, Landon
Barnes, Stephen
Srivastava, Kiran
Joseph, Roy
αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
title αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
title_full αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
title_fullStr αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
title_full_unstemmed αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
title_short αA and αB peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
title_sort αa and αb peptides from human cataractous lenses show antichaperone activity and enhance aggregation of lens proteins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9744240/
https://www.ncbi.nlm.nih.gov/pubmed/36540064
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