Research Paper Volume 11, Issue 23 pp 11268—11313

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Figure 6. Comparison of the oxidative stress and DNA damage RXFP3 interactome indicates roles in age-related processes. Using the specific and consistent peroxide (A, B) and CPT-induced (C, D) RXFP3 interactome datasets we investigated the potential of these proteins to form a network using NetworkAnalyst. To generate statistically-significant interaction network KEGG enrichment (A and C) and Gene Ontology – Biological process (B and D) analysis were performed. Using both generic and hypothalamus-specific backgrounds resulted in highly similar enriched GO terms and KEGG pathways. Using the peroxide-induced RXFP3 interactome we found that the interacting protein network was (A) strongly associated with DNA protection management, cell cycle control, energy metabolism, and lifespan at the KEGG pathways level, (B) while at the GO biological annotation, we also see a strong connection to DNA integrity management, and additional age-associated oxidative damage. (C) Using the same KEGG pathways analysis on the CPT-induced interactome we again found a strong network phenotype associated with aging, i.e. cell cycle control, and age-related tissue pathology. (D) GO biological process analysis showed a strong association with pathological aging responses, such as energy diversification and stress resilience.