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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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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