PMID- 16517499 OWN - NLM STAT- MEDLINE DCOM- 20060510 LR - 20131121 IS - 1071-5762 (Print) IS - 1029-2470 (Linking) VI - 40 IP - 4 DP - 2006 Apr TI - Broad-spectrum antioxidant peptides derived from His residue-containing sequences present in human paraoxonase 1. PG - 349-58 AB - Hydroxyl or peroxyl radicals and hypochlorous acid (HOCl) are known to cause the oxidation of lipoproteins. Here, we examined Cu(2+)-binding property of paraoxonase 1 (PON1), and antioxidant actions of peptides, resembling His residue-containing sequences in PON1, against oxidations by Cu(2+), peroxyl radicals or HOCl. When Cu(2+)-binding property of PON1 was examined spectrophotometrically, the maximal Cu(2+) binding was achieved at 1:1 molar ratio of PON1: Cu(2+). Additionally, Cu(2+)-catalyzed oxidative inactivation of PON1 was prevented by Ca(2+)-depleted PON1 at 1:1 ratio, but not diethylpyrocarbonate (DEPC)-modified PON1, suggesting the participation of His residue in Cu(2+)-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 Cu(2+)-mediated low density lipoprotein (LDL) oxidation and PON1 inactivation. Especially, FHKALY, FHKY or NHP efficiently prevented Cu(2+)-induced LDL oxidation (24 h), indicating a tight binding of Cu(2+) by peptides. In support of this, the peptide/Cu(2+) 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 Cu(2+), 2,2'-azobis-2-amidinopropane hydrochloride (AAPH) or HOCl. FAU - Nguyen, Su Duy AU - Nguyen SD AD - College of Pharmacy, Chungnam National University, Yuseong-Ku, Taejon 305 764, South Korea. FAU - Jeong, Tae-Sook AU - Jeong TS FAU - Kim, Mee Ree AU - Kim MR FAU - Sok, Dai-Eun AU - Sok DE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Free Radic Res JT - Free radical research JID - 9423872 RN - 0 (Antioxidants) RN - 0 (Lipoproteins) RN - 0 (Oxidants) RN - 0 (Peptides) RN - 0 (Peroxides) RN - 3170-83-0 (perhydroxyl radical) RN - 4QD397987E (Histidine) RN - 789U1901C5 (Copper) RN - EC 3.1.8.1 (Aryldialkylphosphatase) RN - EC 3.1.8.1 (PON1 protein, human) SB - IM MH - Antioxidants/*chemical synthesis/chemistry/metabolism MH - Aryldialkylphosphatase/*chemistry/metabolism MH - Copper/metabolism MH - Histidine/*chemistry MH - Humans MH - Lipoproteins/metabolism MH - Oxidants/metabolism MH - Oxidation-Reduction MH - Peptides/*chemical synthesis/*chemistry/metabolism MH - Peroxides/metabolism EDAT- 2006/03/07 09:00 MHDA- 2006/05/11 09:00 CRDT- 2006/03/07 09:00 PHST- 2006/03/07 09:00 [pubmed] PHST- 2006/05/11 09:00 [medline] PHST- 2006/03/07 09:00 [entrez] AID - H13U20870KKU3658 [pii] AID - 10.1080/10715760500534429 [doi] PST - ppublish SO - Free Radic Res. 2006 Apr;40(4):349-58. doi: 10.1080/10715760500534429.