クルクミン類似体GO-Y022は心機能低下を改善した

• Published in: 日本薬理学会年会要旨集 p. 3-B-P-214
• Main Authors: 平子, 裕太, 砂川, 陽一, 清水, 果奈, 船本, 雅文, 刀坂, 泰史, 浜辺, 俊英, 柴田, 浩之, 小見山, 麻紀, 長谷川, 浩二, 森本, 達也
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: cardiac myocyte; heart; hypertrophy; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_3-B-P-214

【Introduction】We previously found that a natural p300 HAT inhibitor, curcumin (CUR), can inhibit cardiomyocyte hypertrophy and the development of heart failure in vivo. We focused on a CUR analog, GO-Y022, which shows stronger anti-cancer activity than CUR. The purpose of this study was to determine whether GO-Y022 inhibits p300-HAT activity and can be used as a therapeutic agent for heart failure. 【Methods & Results】In vitro HAT assay using recombinant p300-HAT domain showed that GO-Y022 inhibited p300-HAT activity as well as CUR. Primary cultured cardiomyocytes prepared from neonatal rats were treated with GO-Y022 or CUR and then stimulated with phenylephrine (PE) for 48 hours. One µM of GO-Y022 suppressed PE-induced histone H3K9 acetylation, hypertrophic response gene transcription, and cardiomyocyte hypertrophy to the same extent as 10 µM of CUR. C57BL/6j male mice were subjected to transverse aortic constriction (TAC) or sham operation. The TAC mice were randomly assigned to five groups: Vehicle, CUR at 1 or 50 mg/kg, or GO-Y022 at 0.2 or 1 mg/kg. After 8 weeks daily oral treatment, echocardiographic analysis showed that 1 mg/kg of GO-Y022 and 50 mg/kg of CUR improved a TAC-induced increase in left ventricular posterior wall thickness and a decrease in fractional shortening.【Conclusion】These results indicate that GO-Y022 strongly inhibits both PE-induced hypertrophic responses and pressure overload-induced development of heart failure. These findings suggest that GO-Y022 may be a novel candidate agent for heart failure therapy.