Oxidative proteome modifications target specific cellular pathways during oxidative stress, cellular senescence and
Martin A Baraibar1, Bertrand Friguet
1Laboratoire de Biologie Cellulaire du Vieillissement, UR4-IFR83, Université Pierre et Marie Curie-Paris 6, 4 place Jussieu, 75252 Paris Cedex 05, France.
Protein damage from oxidative stress increases with age, impacting cellular functions and contributing to age-related diseases. This study identifies key pathways affected by these modifications.
Area of Science:
- Biochemistry
- Cell Biology
- Gerontology
Background:
- Aging is associated with increased reactive oxygen species and toxic compounds.
- Failure in protein maintenance contributes to age-related damaged protein accumulation.
- Oxidative modifications affect proteins involved in crucial cellular functions.
Purpose of the Study:
- To investigate the accumulation and pathways of oxidatively modified proteins during aging.
- To analyze proteome alterations in human muscle adult stem cells under oxidative stress.
- To build a database of proteins modified by carbonylation, glycation, and lipid peroxidation in aging and disease.
Main Methods:
- Analysis of senescent human WI-38 fibroblasts.
- Proteomic analysis of human muscle adult stem cells under oxidative stress.
- Database construction of modified proteins in aging and age-related diseases.
Main Results:
- Oxidized proteins, lipid peroxidation, and glycoxidation adducts accumulate in senescent cells.
- Modified proteins are primarily involved in protein maintenance, energy metabolism, and cytoskeleton.
- Carbonylated proteins in stem cells impact carbohydrate metabolism, protein maintenance, motility, and homeostasis.
- Common metabolic pathways are targeted by these modifications across different tissues.
Conclusions:
- Irreversible oxidative protein modifications have deleterious effects on key cellular pathways during aging.
- These modifications are implicated in the pathogenesis of age-related diseases.
- Understanding these pathways is crucial for addressing aging and related diseases.
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