Micelle-associated endomorphin-1 has ability to bind copper in the oxidation state either Cu(II) or Cu(I)
2022
Kuwana, Yusuke | Ashizawa, Yuya | Ajima, Miki | Nomura, Takuya | Kakeno, Mayu | Hirai, Shunya | Miura, Takashi
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.
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