Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry

The lenticular fiber cells are comprised of extremely long-lived proteins while still maintaining an active biochemical state. Dysregulation of these activities has been implicated in diseases such as age-related cataracts. However, the lenticular protein dynamics underlying health and disease is un...

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Main Authors: Pan Liu, Seby Louis Edassery, Laith Ali, Benjamin R Thomson, Jeffrey N Savas, Jing Jin
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-12-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/50170
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spelling doaj-3ca3af7863aa408a8b3a22e686acd5422021-05-05T18:10:19ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.50170Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometryPan Liu0https://orcid.org/0000-0002-3066-652XSeby Louis Edassery1Laith Ali2Benjamin R Thomson3https://orcid.org/0000-0001-6565-5866Jeffrey N Savas4https://orcid.org/0000-0002-8173-5580Jing Jin5https://orcid.org/0000-0001-7023-5305Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, United StatesDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesFeinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, United StatesDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United StatesFeinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, United StatesThe lenticular fiber cells are comprised of extremely long-lived proteins while still maintaining an active biochemical state. Dysregulation of these activities has been implicated in diseases such as age-related cataracts. However, the lenticular protein dynamics underlying health and disease is unclear. We sought to measure the global protein turnover rates in the eye using nitrogen-15 labeling of mice and mass spectrometry. We measured the 14N/15N-peptide ratios of 248 lens proteins, including Crystallin, Aquaporin, Collagen and enzymes that catalyze glycolysis and oxidation/reduction reactions. Direct comparison of lens cortex versus nucleus revealed little or no 15N-protein contents in most nuclear proteins, while there were a broad range of 14N/15N ratios in cortex proteins. Unexpectedly, like Crystallins, many enzymes with relatively high abundance in nucleus were also exceedingly long-lived. The slow replacement of these enzymes in spite of young age of mice suggests their potential roles in age-related metabolic changes in the lens.https://elifesciences.org/articles/50170stable isotope labeling in mammals (SILAM)protein turnovereye proteomics
collection DOAJ
language English
format Article
sources DOAJ
author Pan Liu
Seby Louis Edassery
Laith Ali
Benjamin R Thomson
Jeffrey N Savas
Jing Jin
spellingShingle Pan Liu
Seby Louis Edassery
Laith Ali
Benjamin R Thomson
Jeffrey N Savas
Jing Jin
Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
eLife
stable isotope labeling in mammals (SILAM)
protein turnover
eye proteomics
author_facet Pan Liu
Seby Louis Edassery
Laith Ali
Benjamin R Thomson
Jeffrey N Savas
Jing Jin
author_sort Pan Liu
title Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
title_short Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
title_full Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
title_fullStr Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
title_full_unstemmed Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
title_sort long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2019-12-01
description The lenticular fiber cells are comprised of extremely long-lived proteins while still maintaining an active biochemical state. Dysregulation of these activities has been implicated in diseases such as age-related cataracts. However, the lenticular protein dynamics underlying health and disease is unclear. We sought to measure the global protein turnover rates in the eye using nitrogen-15 labeling of mice and mass spectrometry. We measured the 14N/15N-peptide ratios of 248 lens proteins, including Crystallin, Aquaporin, Collagen and enzymes that catalyze glycolysis and oxidation/reduction reactions. Direct comparison of lens cortex versus nucleus revealed little or no 15N-protein contents in most nuclear proteins, while there were a broad range of 14N/15N ratios in cortex proteins. Unexpectedly, like Crystallins, many enzymes with relatively high abundance in nucleus were also exceedingly long-lived. The slow replacement of these enzymes in spite of young age of mice suggests their potential roles in age-related metabolic changes in the lens.
topic stable isotope labeling in mammals (SILAM)
protein turnover
eye proteomics
url https://elifesciences.org/articles/50170
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