Novel compounds protect auditory hair cells against gentamycin-induced apoptosis by maintaining the expression level of H3K4me2

Drug Delivery
Ao LiH Li

Abstract

Aminoglycoside-induced hair cell (HC) loss is a major cause of hearing impairment, and the effective prevention of HC loss remains an unmet medical need. Epigenetic mechanisms have been reported to be involved in protecting cochlear cells against ototoxic drug injury, and in this study we developed new bioactive compounds that have similar chemical structures as the epigenetics-related lysine-specific demethylase 1 (LSD1) inhibitors. LSD1 inhibitors have been reported to protect cochlear cells by preventing demethylation of dimethylated histone H3K4 (H3K4me2). To determine whether these new compounds exert similar protective effects on HCs, we treated mouse cochlear explant cultures with the new compounds together with gentamycin. There was a severe loss of HCs in the organ of Corti after gentamycin exposure, while co-treatment with the new compounds significantly protected against gentamycin-induced HC loss. H3K4me2 levels in the nuclei of HCs decreased after exposure to gentamycin, but H3K4me2 levels were maintained in the presence of the new compounds. Apoptosis is also involved in the injury process, and the new compounds protected the inner ear HCs against apoptosis by reducing caspase-3 activation. Together, our findings ...Continue Reading

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Citations

Aug 23, 2019·World Journal of Gastrointestinal Oncology·Hong-Ming PanXiao-Ling Li
Jan 9, 2021·Cell Death & Disease·Tong ZhaoQing Yin Zheng
Mar 12, 2021·Frontiers in Cell and Developmental Biology·Jun LvRenjie Chai
Mar 19, 2021·Frontiers in Cell and Developmental Biology·Lili XiaoYanmei Feng
Jul 22, 2021·Oxidative Medicine and Cellular Longevity·Yanzhuo ZhangBaoshan Wang
Jul 27, 2021·Neural Plasticity·Chang LiuYingzi He
Aug 3, 2021·Neural Plasticity·Peng WuHe Li
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Siyu LiXia Gao
Aug 27, 2021·Cell Biology International·Xiaoyu YuYong Li
Sep 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yushi HayashiAlbert S B Edge
Oct 9, 2021·Frontiers in Cell and Developmental Biology·Tingting DongMin Lu
Oct 26, 2021·Frontiers in Cell and Developmental Biology·Yi-Ming ZhuXiang-Ping Li
Dec 7, 2021·Frontiers in Cell and Developmental Biology·Xiaomin TangJingwu Sun

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Methods Mentioned

BETA
cochlear explant

Software Mentioned

SigmaPlot

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