A novel quinone derived from 5-hydroxyindoleacetic acid reacts with protein: Possible participation of oxidation of serotonin and its metabolite in the development of atherosclerosis

作者：Kato Yoji^*; Oki Kota; Suga Naoko; Ono Shigeki; Ishisaka Akari; Miura Yoko; Kanazawa Satoshi; Naito Michitaka; Kitamoto Noritoshi; Kettle Anthony J

来源：Free Radical Biology and Medicine, 2016, 101: 500-510.

DOI：10.1016/j.freeradbiomed.2016.11.023

• Quinone
• 5-Hydroxyindoleacetic acid
• Serotonin
• Antibody
• Atherosclerosis

The modification of 5-hydroxyindoleacetic acid (5HIAA) by myeloperoxidase with a xanthine oxidase system was investigated by chromatographic analyses. Two major products were identified as a dimer and quinone (indoleacetate dione) of 5HIAA. The formation of a quinone moiety was also confirmed by chemical trapping with o-phenylenediamine. In the presence of N-acetyl-cysteine (NAC), a quinone-NAC adduct was formed. When glyceraldehyde 3-phosphate dehydrogenase was exposed to the myeloperoxidase system with 5HIAA, quinone adducts were formed on the protein molecule. A monoclonal antibody was prepared using a quinone-modified protein as an immunogen to immunochemically detect the quinone on a protein. The established antibody recognized the quinone-NAC adduct, quinone-modified poly-L-lysine, and quinone-modified low-density lipoprotein. Quinone-modified proteins in human atherosclerotic lesions were immunohistochemically observed using the established antibody to the quinone and also a monoclonal antibody to tryptamine dione-modified protein, suggesting an occurrence of in vivo oxidation of serotonin and 5HIAA, accompanied by covalent adduction to biomolecules.

• 出版日期2016-12