The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage
| Autor: | Hanne Leysen, Stuart Maudsley, Jaana van Gastel, Paula Santos-Otte, Jhana O. Hendrickx, Abdelkrim Azmi, Bronwen Martin |
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| Rok vydání: | 2019 |
| Předmět: |
Aging
DNA damage medicine.disease_cause Receptors G-Protein-Coupled GPCR medicine Humans Gene Regulatory Networks RNA Messenger Receptor Biology G protein-coupled receptor Relaxin Felodipine Chemistry GTPase-Activating Proteins relaxin 3 Computational Biology Cell Biology Cell biology Oxidative Stress HEK293 Cells Gene Expression Regulation Phosphorylation Camptothecin Human medicine Topoisomerase I Inhibitors relaxin family peptide 3 receptor Relaxin-3 Oxidative stress Research Paper medicine.drug |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.102528 |
| Popis: | DNA damage response (DDR) processes, often caused by oxidative stress, are important in aging and -related disorders. We recently showed that G protein-coupled receptor (GPCR) kinase interacting protein 2 (GIT2) plays a key role in both DNA damage and oxidative stress. Multiple tissue analyses in GIT2KO mice demonstrated that GIT2 expression affects the GPCR relaxin family peptide 3 receptor (RXFP3), and is thus a therapeutically-targetable system. RXFP3 and GIT2 play similar roles in metabolic aging processes. Gaining a detailed understanding of the RXFP3-GIT2 functional relationship could aid the development of novel anti-aging therapies. We determined the connection between RXFP3 and GIT2 by investigating the role of RXFP3 in oxidative stress and DDR. Analyzing the effects of oxidizing (H2O2) and DNA-damaging (camptothecin) stressors on the interacting partners of RXFP3 using Affinity Purification-Mass Spectrometry, we found multiple proteins linked to DDR and cell cycle control. RXFP3 expression increased in response to DNA damage, overexpression, and Relaxin 3-mediated stimulation of RXFP3 reduced phosphorylation of DNA damage marker H2AX, and repair protein BRCA1, moderating DNA damage. Our data suggests an RXFP3-GIT2 system that could regulate cellular degradation after DNA damage, and could be a novel mechanism for mitigating the rate of age-related damage accumulation. |
| Databáze: | OpenAIRE |
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