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.
Highlights
The lens is a transparent body with an essential role in visual acuity
A single layer of germinal cells beneath the anterior capsule gives rise to transitional cells which differentiate into elongating fiber cells and the mature lenticular fiber cells forming the nuclear mass of the lens
While the determination of lack of 15N peptides is subjected to MS detection sensitivity, we listed only the most abundant proteins with the total absence of 15N labels (Figure 2B). These extremely long-lived proteins included structural proteins such as PE-binding protein 1 (PEBP-1), b-Catenin, Moesin, and enzymes that are involved in oxidoreduction such as Peroxiredoxin-2 (Prdx2), Farnesyl pyrophosphate synthase (FPS) and Aldehyde dehydrogenase (Aldh7A), and in glycolysis such as ATP-dependent 6-phosphofructokinase (ATP-PFK)
Summary
The lens is a transparent body with an essential role in visual acuity It consists of an outer capsule of type IV collagen-laminin membrane, the cortex of lens epithelium, and denuclearized and organellefree fiber cells at the core. A single layer of germinal cells beneath the anterior capsule gives rise to transitional cells which differentiate into elongating fiber cells and the mature lenticular fiber cells forming the nuclear mass of the lens. In this process, the human lens continues to grow slowly in its weight and size throughout life (Vavvas et al, 2002; Guirou et al, 2013; Augusteyn, 2007; Bassnett, 2002). Despite the slow turnover of the lens tissue, it remains a site of biochemical activity (Reddy and Giblin, 1984; Hejtmancik et al, 2015), in which the production of reducing metabolites and perhaps local enzymatic reactions within the fiber cells are important in combating oxidative stress
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