BETA.-Citryl-L-glutamate Is an Endogenous Iron Chelator That Occurs Naturally in the Developing Brain
| Autor: | Masaharu Miyake, Masanori Narahara, Makiko Kouda, Kaori Matsuyama, Tatsuya Hasegawa, Michiko Hamada-Kanazawa, Kiyoka Kanazawa, Akira Odani |
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| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
DNA damage Iron Metal ions in aqueous solution Pharmaceutical Science Iron Chelating Agents Ferric Compounds Medicinal chemistry Antioxidants Metal chemistry.chemical_compound Glutamates Animals Chelation Ferrous Compounds Rats Wistar Pharmacology chemistry.chemical_classification Reactive oxygen species Deoxyribose Brain General Medicine Hydrogen-Ion Concentration Rats Molecular Weight Solubility chemistry Metals Stability constants of complexes visual_art visual_art.visual_art_medium Cattle Titration Reactive Oxygen Species DNA Damage Plasmids |
| Zdroj: | Biological and Pharmaceutical Bulletin. 33:729-737 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.33.729 |
| Popis: | The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from developing brains, while it has also been found in high concentrations in testes and eyes. However, its functional roles are unclear. To evaluate its coordination with metal ions, we performed pH titration experiments. The stability constant, logbeta(pqr) for M(p)(beta-CG)(q)H(r) was calculated from pH titration data, which showed that beta-CG forms relatively strong complexes with Fe(III), Cu(II), Fe(II) and Zn(II). beta-CG was also found able to solubilize Fe more effectively from Fe(OH)(2) than from Fe(OH)(3). Therefore, we examined the effects of beta-CG on Fe-dependent reactive oxygen species (ROS)-generating systems, as well as the potential ROS-scavenging activities of beta-CG and metal ion-(beta-CG) complexes. beta-CG inhibited the Fe-dependent degradation of deoxyribose and Fe-dependent damage to DNA or plasmid DNA in a dose-dependent manner, whereas it had no effect on Cu-mediated DNA damage. In addition, thermodynamic data showed that beta-CG in a physiological pH solution is an Fe(II) chelator rather than an Fe(III) chelator. Taken together, these findings suggest that beta-CG is an endogenous low molecular weight Fe chelator. |
| Databáze: | OpenAIRE |
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