title: Royal Jelly Constituents Increase the Expression of Extracellular Superoxide Dismutase through Histone Acetylation in Monocytic THP-1 Cells.
abstract: Extracellular superoxide dismutase (EC-SOD) is one of the main SOD isozymes and plays an important role in the prevention of cardiovascular diseases by accelerating the dismutation reaction of superoxide. Royal jelly includes 10-hydroxy-2-decenoic acid (10H2DA, 2), which regulates the expression of various types of genes in epigenetics through the effects of histone deacetylase (HDAC) antagonism. The expression of EC-SOD was previously reported to be regulated epigenetically through histone acetylation in THP-1 cells. Therefore, we herein evaluated the effects of the royal jelly constituents 10-hydroxydecanoic acid (10HDA, 1), sebacic acid (SA, 3), and 4-hydroperoxy-2-decenoic acid ethyl ester (4-HPO-DAEE, 4), which is a derivative of 2, on the expression of EC-SOD in THP-1 cells. The treatment with 1 mM 1, 2, or 3 or 100 μM 4 increased EC-SOD expression and histone H3 and H4 acetylation levels. Moreover, the enrichment of acetylated histone H4 was observed in the proximal promoter region of EC-SOD and was caused by the partial promotion of ERK phosphorylation (only 4) and inhibition of HDAC activities, but not by the expression of HDACs. Overall, 4 exerted stronger effects than 1, 2, or 3 and has potential as a candidate or lead compound against atherosclerosis.
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Makino
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Ogasawara
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Mitsugi
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yamaguchi
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Akichika
authors.initials: A
authors.lastname: Itoh
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, and ‡Department of Organic and Medicinal Chemistry, Laboratory of Pharmaceutical Synthetic Chemistry, Gifu Pharmaceutical University , 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D005227:Fatty Acids / Q000737:chemistry* / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000099219:Royal Jelly
chemical_list: D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D006877:Hydroxamic Acids; D007659:Ketones; D013482:Superoxide Dismutase; D000099219:Royal Jelly; C113994:4-hydroxy-1-phenyl-1-octanone; C055444:4-decenoic acid; C052476:2-decenoic acid; C055543:10-hydroxy-2-decenoic acid