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

Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data file (Supplementary data set) have been provided.

The following data sets were generated

Article and author information

Author details

  1. Pan Liu

    Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3066-652X
  2. Seby Louis Edassery

    Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Laith Ali

    Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin R Thomson

    Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6565-5866
  5. Jeffrey N Savas

    Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    For correspondence
    jeffrey.savas@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8173-5580
  6. Jing Jin

    Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, United States
    For correspondence
    jing.jin@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7023-5305

Funding

National Institutes of Health (R01AG061787)

  • Jeffrey N Savas

National Institutes of Health (R21AI131087)

  • Jing Jin

National Institutes of Health (R01EY025799)

  • Jing Jin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Ethics

Animal experimentation: All animal procedures were approved by Institutional Animal Care and Use Committee of the Northwestern University (approved protocol number IS00000429 and IS00000862).

Version history

  1. Received: July 12, 2019
  2. Accepted: December 4, 2019
  3. Accepted Manuscript published: December 10, 2019 (version 1)
  4. Version of Record published: December 16, 2019 (version 2)

Copyright

© 2019, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Pan Liu
  2. Seby Louis Edassery
  3. Laith Ali
  4. Benjamin R Thomson
  5. Jeffrey N Savas
  6. Jing Jin
(2019)
Long-lived metabolic enzymes in the Crystallin lens identified by pulse-labeling of mice and mass spectrometry
eLife 8:e50170.
https://doi.org/10.7554/eLife.50170

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https://doi.org/10.7554/eLife.50170