Micelle-associated endomorphin-1 has ability to bind copper in the oxidation state either Cu(II) or Cu(I)
Micelle-associated endomorphin-1 has ability to bind copper in the oxidation state either Cu(II) or Cu(I)
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胶束相关内吗啡肽-1 能够结合氧化态铜 Cu(II) 或 Cu(I)
DOI：
10.1016/j.abb.2022.109305
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发表时间：
2022
影响因子：
3.9
通讯作者：
Miura Takashi
中科院分区：
文献类型：
--
作者：
Kuwana Yusuke;Ashizawa Yuya;Ajima Miki;Nomura Takuya;Kakeno Mayu;Hirai Shunya;Miura Takashi
在氧化的细胞外环境中，Cu（II）还原为Cu(I)是神经退行性疾病的潜在危险因素，因为Cu(I)再氧化为Cu（II）可以与活性氧的产生相耦合。然而，人们对大脑如何免受铜诱导的氧化应激的影响知之甚少。本研究研究了内源性阿片肽内啡肽-1 （EM1, tyr - pro - trp - ph - nh2）与离子铜的相互作用。EM1不能用普通的金属配位化学与铜结合，因为EM1与金属离子的螯合络合物的形成被第二位置的脯氨酸残基所抑制。然而，在SDS胶束存在的情况下，在添加铜离子（Cu（II）或Cu(I)）时，观察到EM1色氨酸侧链的荧光显著猝灭。仅在胶束存在的情况下，在EM1中加入铜也会引起色氨酸紫外吸收光谱的变化，这是阳离子-π相互作用的诊断。用丙氨酸取代Tyr1后，铜诱导的荧光和紫外吸收光谱变化消失。结果表明，EM1通过Tyr1和Trp3芳香侧链的π电子与铜离子结合，并以胶束结合形式紧密接触。铜催化的氧化/还原反应过程将多巴胺转化为神经黑色素，这涉及潜在的神经毒性中间体，被EM1抑制。由于能够结合Cu（II）和Cu(I)， EM1可能具有抑制大脑中铜介导的氧化应激的潜力。目前的结果表明，EM1的抗氧化作用，不同于其已知的镇痛作用。
Reduction of Cu(II) to Cu(I) in an oxidizing extracellular environment is a potential risk factor for neurodegenerative diseases, because the re-oxidation of Cu(I) to Cu(II) can be coupled to generation of reactive oxygen species. However, little is known about how the brain is protected from the copper-induced oxidative stress. In the present study, interactions of the endogenous opioid peptide endomorphin-1 (EM1, Tyr-Pro-Trp-Phe-NH2) with ionic copper were investigated. EM1 cannot bind copper with ordinary metal coordination chemistry, since the chelate complex formation of EM1 with the metal ion is inhibited by the proline residue in the second position. In the presence of SDS micelles, however, a significant quenching of fluorescence of the tryptophan side chain of EM1 was observed on addition of copper ion, either Cu(II) or Cu(I). The spectral changes of the UV absorption of the tryptophan, which are diagnostic of cation–π interaction, were also brought about by addition of copper to EM1 only in the presence of micelles. The copper-induced spectral changes of both fluorescence and UV absorption disappeared upon the substitution of Tyr1 with alanine. The obtained results indicated that EM1 binds the copper ion through the π-electrons of aromatic side chains of Tyr1 and Trp3, which are in close contact each other in the micelle-associated form. The copper-catalyzed oxidation/reduction reaction process converting dopamine to neuromelanin, which involves potentially neurotoxic intermediates, is inhibited by EM1. Owing to the ability to bind both Cu(II) and Cu(I), EM1 may have the potential to suppress the copper-mediated oxidative stress in the brain. The present results suggest an antioxidative effect of EM1, distinct from its known analgesic effect.