Epigallocatechin-3-gallate restores mitochondrial homeostasis impairment by inhibiting HDAC1-mediated NRF1 histone deacetylation in cardiac hypertrophy

作者全名："Li, Gu; Pan, Bo; Liu, Lifei; Xu, Xiaohui; Zhao, Weian; Mou, Qiuhong; Hwang, Narae; Chung, Su Wol; Liu, Xiaoli; Tian, Jie"

作者地址："[Li, Gu; Pan, Bo; Xu, Xiaohui; Zhao, Weian; Mou, Qiuhong; Tian, Jie] Chongqing Med Univ, Dept Cardiol, Childrens Hosp, Chongqing, Peoples R China; [Li, Gu; Pan, Bo; Liu, Lifei; Xu, Xiaohui; Zhao, Weian; Mou, Qiuhong; Tian, Jie] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Li, Gu; Hwang, Narae; Chung, Su Wol; Liu, Xiaoli] Brigham & Womens Hosp, Harvard Med Sch, Dept Pediat Newborn Med, Boston, MA USA"

通信作者："Tian, J (通讯作者)，Chongqing Med Univ, Dept Cardiol, Childrens Hosp, Chongqing, Peoples R China.; Tian, J (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China."

来源：MOLECULAR AND CELLULAR BIOCHEMISTRY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000998653700001

JCR分区：Q3

影响因子：3.5

年份：2023

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期号：　

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文献类型：Article; Early Access

关键词：NRF1; HDAC1; EGCG; Histone acetylation; Mitochondrial homeostasis; Hypertrophy

摘要："Decompensated cardiac hypertrophy is accompanied by impaired mitochondrial homeostasis, whether histone acetylation is involved in this process is yet to be determined. The role of HDAC1-mediated NRF1 histone deacetylation was investigated in transverse aortic constriction (TAC)-induced hypertrophy in rats and phenylephrine (PE)-induced hypertrophic cardiomyocytes. Administration of epigallocatechin-3-gallate (EGCG), an inhibitor of HDAC1, restored cardiac function, decreased heart/body weight and fibrosis, increased the ratio of mtDNA/nDNA and the percentage of LysoTracker(+) CMs in TAC, compared with TAC without receiving EGCG. In PE-treated hypertrophic H9C2 cells, EGCG attenuated cell hypertrophy and increased LC3B II(+)MitoTracker(+) puncta, as well as the ratio of mtDNA/nDNA. Interestingly, NRF1 but not PGC-1 alpha expression was decreased in TAC- or PE-induced hypertrophic hearts or cells, respectively, while EGCG upregulated both NRF1 and PGC-1 alpha in vitro. EGCG treatment also increased the interaction between PGC-1 alpha and NRF1. In addition to inhibiting HDAC1 expression, EGCG decreased the binding of HDAC1 and increased the binding of acH3K9 or acH3K14 in the promotor regions of PGC-1 alpha and NRF1. In neonatal rat cardiomyocytes, restored NRF1, TFAM and FUNDC1 were abolished by the overexpression of HDAC1. Collectively, data suggest that NRF1 reduction was averted by EGCG via inhibiting HDAC1-mediated histone deacetylation. Acetylation of NRF1 histone may play a key role in maintaining mitochondrial homeostasis associated with cardiac hypertrophy."

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