Long-lived proteins and DNA as candidate predictive biomarkers for tissue associated diseases

ABSTRACT: Protein turnover, the result of protein synthesis and degradation, is an important mechanism to preserve cellular integrity. The majority of cellular proteins are broken down over a period of hours to weeks to prevent a buildup of proteins that lose their function due to damage caused by misfolding, modifications or degradation. Only a small fraction of the proteome is long-lived. In the current study we have subjected mice to in vivo stable isotope labeling starting at birth until postnatal day 89. Proteins from ten tissues and plasma were then analyzed by shotgun proteomics and interrogated for long-lived proteins (LLPs) by subjecting mass spectra to a database search for non-labeled proteins which yielded 2113 LLPs identifications from 10 mouse tissues. These proteins differed between tissues, with some shared by almost all tissues. Interestingly, a significant percentage of LLPs was detected in plasma. The accumulation of these LLPs may contribute to age-related cardiovascular and other diseases. LLPs identified in the brain were related to neurodegenerative diseases. The relative quantification of non-labeled and labeled DNA-derived deoxynucleosides from the same tissues by mass spectrometry provided information about DNA cellular renewal and showed good correlation with LLPs in the brain. The combined data reveal tissue-specific maps of mouse LLPs that may be involved in pathology due to their low degree of renewal and the resulting increased risk for incurring damage. Tissue-derived peripheral LLPs have potential to serve as biomarkers for aging and age-related disease.

ORGANISM(S): Mus Musculus

SUBMITTER: Yaoyang Zhang  

PROVIDER: PXD050843 | iProX | Thu Mar 21 00:00:00 GMT 2024

REPOSITORIES: iProX