Investigation of metal modulation of oxytocin structure receptor-mediated signaling.
Investigation of metal modulation of oxytocin structure receptor-mediated signaling.
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DOI：
10.1039/d2cb00225f
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发表时间：
2023-02-08
影响因子：
4.1
通讯作者：
Heffern, Marie C.
中科院分区：
文献类型：
--
作者：
O'Sullivan, Justin J.;Uyeda, Kylie S.;Stevenson, Michael J.;Heffern, Marie C.
催产素是一种9氨基酸肽激素。自1954年发现以来，它最常被研究的是其在刺激分娩和哺乳方面的作用。然而，现在已知催产素在整个身体中具有广泛多样的功能，包括神经调节，骨骼生长和炎症。先前的研究表明，催产素活性可能需要二价金属离子，但确切的金属种类和具体途径尚未完全阐明。在这项工作中，我们专注于通过远紫外圆二色性表征铜和锌结合形式的催产素和相关类似物。我们报告说，铜（II）和锌（II）结合独特的催产素和所有类似物的调查。此外，我们调查这些金属结合形式可能会影响下游信号的MAPK激活受体结合后。我们发现，Cu（II）和Zn（II）结合催产素减弱MAPK途径的激活受体结合后，相对于单独的催产素。有趣的是，我们观察到，锌（ii）结合形式的线性催产素促进增加MAPK信号。本研究为进一步阐明金属对催产素生物活性的影响奠定了基础。催产素和类似物库显示在催产素受体表达的HEK293细胞中MAPK活化的金属依赖性调节。
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. Oxytocin and a library of analogs show metal-dependent modulation of MAPK activation in oxytocin-receptor-expressing HEK293 cells.
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影响因子：
4.1
作者：
Chatterjee, Oishi;Patil, Krutika;Prasad, T. S. Keshava
通讯作者：
Prasad, T. S. Keshava
影响因子：
--
作者：
Antosiewicz, Jan M;Shugar, David
通讯作者：
Shugar, David
影响因子：
2.9
作者：
Joly, Laure;Antoine, Rodolphe;Dugourd, Philippe
通讯作者：
Dugourd, Philippe
影响因子：
7
作者：
Mervinetsky, Evgeniy;Alshanski, Israel;Yitzchaik, Shlomo
通讯作者：
Yitzchaik, Shlomo
影响因子：
3.2
作者：
Passoni, I.;Leonzino, M.;Busnelli, M.
通讯作者：
Busnelli, M.