Differential selectivity of protein modification by the cyclopentenone prostaglandins PGA1 and 15-deoxy-Δ12,14-PGJ2:: Role of glutathione

Differential selectivity of protein modification by the cyclopentenone prostaglandins PGA1 and 15-deoxy-Δ12,14-PGJ2:: Role of glutathione
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DOI:
10.1016/j.febslet.2005.09.069
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发表时间:
2005-10-24
期刊:
影响因子:
3.5
通讯作者:
Pérez-Sala, D
Pérez-Sala, D
中科院分区:
生物学3区
文献类型:
--
作者:
Gayarre, J;Stamatakis, K;Pérez-Sala, D

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具有抗肿瘤和抗增殖特性的环戊烯酮类化合物(cyPG)已被设想为开发治疗剂的先导。由于cyPG效应部分通过与关键信号蛋白形成共价加合物介导,因此评估这种相互作用的特异性非常重要。通过使用15-脱氧-Δ(12,14)-PGJ(2)(15 d-PGJ(2)-B)和PGA(1)(PGA(1)-B)的生物素化衍生物,我们在本文中提供了不同cyPG对蛋白质修饰的差异选择性的新证据。15 d-PGJ(2)-B和PGA(1)-B与细胞蛋白结合的显著定量和定性差异与谷胱甘肽(GSH)存在下的体外和完整细胞中的不同反应性有关。因此,GSH水平可能不仅影响cyPG作用的强度,而且影响其特异性。(c)2005年由Elsevier B. V.出版
Cyclopentenone prostaglandins (cyPG) with antiinflammatory and antiproliferative properties have been envisaged as leads for the development of therapeutic agents. Because cyPG effects are mediated in part by the formation of covalent adducts with critical signaling proteins, it is important to assess the specificity of this interaction. By using biotinylated derivatives of 15-deoxy-Delta (12,14)-PGJ(2) (15d-PGJ(2)-B) and PGA(1) (PGA(1)-B) we herein provide novel evidence for the differential selectivity of protein modification by distinct cyPG. The marked quantitative and qualitative differences in the binding of 15d-PGJ(2)-B and PGA(1)-B to cellular proteins were related to a differential reactivity in the presence of glutathione (GSH), both in vitro and in intact cells. Therefore GSH levels may influence not only the intensity but also the specificity of cyPG action. (c) 2005 Published by Elsevier B.V.