Investigation of metal modulation of oxytocin structure receptor-mediated signaling.
| Autor: | O'Sullivan JJ; Department of Chemistry, University of California, Davis Davis CA 95616 USA mcheffern@ucdavis.edu., Uyeda KS; Department of Chemistry, University of California, Davis Davis CA 95616 USA mcheffern@ucdavis.edu., Stevenson MJ; Department of Chemistry, University of California, Davis Davis CA 95616 USA mcheffern@ucdavis.edu., Heffern MC; Department of Chemistry, University of California, Davis Davis CA 95616 USA mcheffern@ucdavis.edu. |
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| Jazyk: | angličtina |
| Zdroj: | RSC chemical biology [RSC Chem Biol] 2023 Jan 04; Vol. 4 (2), pp. 165-172. Date of Electronic Publication: 2023 Jan 04 (Print Publication: 2023). |
| DOI: | 10.1039/d2cb00225f |
| Abstrakt: | Oxytocin is a 9-amino acid peptide hormone. Since its discovery in 1954, it has most commonly been studied in relation to its role in stimulating parturition and lactation. However, it is now known that oxytocin has a widely diverse set of functions throughout the body including neuromodulation, bone growth, and inflammation. Previous research has suggested that divalent metal ions may be required for oxytocin activity, but the exact metal species and specific pathways have yet to be fully elucidated. In this work, we focus on characterizing copper and zinc bound forms of oxytocin and related analogs through far-UV circular dichroism. We report that Cu(ii) and Zn(ii) bind uniquely to oxytocin and all analogs investigated. Furthermore, we investigate how these metal bound forms may affect downstream signaling of MAPK activation upon receptor binding. We find that both Cu(ii) and Zn(ii) bound oxytocin attenuates the activation of the MAPK pathway upon receptor binding relative to oxytocin alone. Interestingly, we observed that Zn(ii) bound forms of linear oxytocin facilitate increased MAPK signaling. This study lays the foundation for future work on elucidating the metal effects on oxytocin's diverse bioactivity. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.) |
| Databáze: | MEDLINE |
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