Broad-spectrum antioxidant peptides derived from His residue-containing sequences present in human paraoxonase 1 |
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Authors: | Nguyen Su Duy Jeong Tae-Sook Kim Mee Ree Sok Dai-Eun |
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Institution: |
a College of Pharmacy, Chungnam National University, Taejon, South Korea
b Lipid metabolism Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon, South Korea
c Department of Food and Nutrition, Chungnam National University, Taejon, South Korea |
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Abstract: | Hydroxyl or peroxyl radicals and hypochlorous acid (HOCl) are known to cause the oxidation of lipoproteins. Here, we examined Cu2+-binding property of paraoxonase 1 (PON1), and antioxidant actions of peptides, resembling His residue-containing sequences in PON1, against oxidations by Cu2+, peroxyl radicals or HOCl. When Cu2+-binding property of PON1 was examined spectrophotometrically, the maximal Cu2+ binding was achieved at 1:1 molar ratio of PON1: Cu2+. Additionally, Cu2+-catalyzed oxidative inactivation of PON1 was prevented by Ca2+-depleted PON1 at 1:1 ratio, but not diethylpyrocarbonate (DEPC)-modified PON1, suggesting the participation of His residue in Cu2+-binding. When His-containing peptides were examined for antioxidant actions, those with either His residue at N-terminal position 2 or 3, or His-Pro sequence at C-terminal remarkably prevented Cu2+-mediated low density lipoprotein (LDL) oxidation and PON1 inactivation. Especially, FHKALY, FHKY or NHP efficiently prevented Cu2+-induced LDL oxidation (24 h), indicating a tight binding of Cu2+ by peptides. In support of this, the peptide/Cu2+ complexes exhibited a superoxide-scavenging activity. Separately, in oxidations by 2,2'-azobis-2-amidinopropane hydrochloride or HOCl, the presence of Tyrosine (Tyr) or Cysteine (Cys) residue markedly enhanced antioxidant action of His-containing peptides. These results indicate that His-containing peptides with Tys or Cys residues correspond to broad spectrum antioxidants in oxidation models employing Cu2+, 2,2'-azobis-2-amidinopropane hydrochloride (AAPH) or HOCl. |
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Keywords: | PON1 peptide LDL oxidation Cu2 hydroxyl radicals |
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