Differential regulation of DNA methylation versus histone acetylation in cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism

被引:48
|
作者
Chaturvedi, Pankaj [1 ]
Kalani, Anuradha [1 ]
Givvimani, Srikanth [1 ]
Kamat, Pradip Kumar [1 ]
Familtseva, Anastasia [1 ]
Tyagi, Suresh C. [1 ]
机构
[1] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40202 USA
关键词
cardiomyocytes; hyperhomocysteinemia; histone modification; DNA methylation; microRNA; CARDIAC-SPECIFIC DELETION; PLASMA HOMOCYSTEINE; OXIDATIVE STRESS; NMDA RECEPTOR; HYPERHOMOCYSTEINEMIA; DYSFUNCTION; RISK; APOPTOSIS; DISEASE; ATRIAL;
D O I
10.1152/physiolgenomics.00168.2013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Differential regulation of DNA methylation versus histone acetylation in cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism. Physiol Genomics 46: 245-255, 2014. First published February 4, 2014; doi:10.1152/physiolgenomics.00168.2013.- The mechanisms of homocysteine-mediated cardiac threats are poorly understood. Homocysteine, being the precursor to S-adenosyl methionine (a methyl donor) through methionine, is indirectly involved in methylation phenomena for DNA, RNA, and protein. We reported previously that cardiac-specific deletion of N-methyl-D-aspartate receptor-1 (NMDAR1) ameliorates homocysteine-posed cardiac threats, and in this study, we aim to explore the role of NMDAR1 in epigenetic mechanisms of heart failure, using cardiomyocytes during hyperhomocysteinemia (HHcy). High homocysteine levels activate NMDAR1, which consequently leads to abnormal DNA methylation vs. histone acetylation through modulation of DNA methyltransferase 1 (DNMT1), HDAC1, miRNAs, and MMP9 in cardiomyocytes. HL-1 cardiomyocytes cultured in Claycomb media were treated with 100 mu M homocysteine in a dose-dependent manner. NMDAR1 antagonist (MK801) was added in the absence and presence of homocysteine at 10 mu M in a dose-dependent manner. The expression of DNMT1, histone deacetylase 1 (HDAC1), NMDAR1, microRNA (miR)- 133a, and miR- 499 was assessed by real-time PCR as well as Western blotting. Methylation and acetylation levels were determined by checking 5=- methylcytosine DNA methylation and chromatin immunoprecipitation. Hyper-homocysteinemic mouse models (CBS +/-) were used to confirm the results in vivo. In HHcy, the expression of NMDAR1, DNMT1, and matrix metalloproteinase 9 increased with increase in H3K9 acetylation, while HDAC1, miR- 133a, and miR- 499 decreased in cardiomyocytes. Similar results were obtained in heart tissue of CBS +/- mouse. High homocysteine levels instigate cardiovascular remodeling through NMDAR1, miR- 133a, miR- 499, and DNMT1. A decrease in HDAC1 and an increase in H3K9 acetylation and DNA methylation are suggestive of chromatin remodeling in HHcy.
引用
收藏
页码:245 / 255
页数:11
相关论文
共 50 条
  • [1] Histone methylation versus histone acetylation: new insights into epigenetic regulation
    Rice, JC
    Allis, CD
    CURRENT OPINION IN CELL BIOLOGY, 2001, 13 (03) : 263 - 273
  • [2] Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation
    Riviere, Guillaume
    Lienhard, Daniel
    Andrieu, Thomas
    Vieau, Didier
    Frey, Brigitte M.
    Frey, Felix J.
    EPIGENETICS, 2011, 6 (04) : 479 - 490
  • [3] Epigenetic markers of tooth eruption - DNA methylation and histone acetylation
    Westerlund, Anna
    Shikhan, Asal
    Sabel, Nina
    Asa'ad, Farah
    Larsson, Lena
    EUROPEAN JOURNAL OF ORAL SCIENCES, 2024, 132 (04)
  • [4] DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers
    Yen, Ching-Yu
    Huang, Hurng-Wern
    Shu, Chih-Wen
    Hou, Ming-Feng
    Yuan, Shyng-Shiou F.
    Wang, Hui-Ru
    Chang, Yung-Ting
    Farooqi, Ammad Ahmad
    Tang, Jen-Yang
    Chang, Hsueh-Wei
    CANCER LETTERS, 2016, 373 (02) : 185 - 192
  • [5] DNA methylation, histone acetylation in the regulation of memory and its modulation during aging
    Singh, Padmanabh
    Paramanik, Vijay
    FRONTIERS IN AGING, 2025, 5
  • [6] Regulation of Opsin Gene Expression by DNA Methylation and Histone Acetylation
    Song, Jin
    VanBuskirk, Julia A.
    Merbs, Shannath L.
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (03)
  • [7] Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses
    Daskalaki, Maria G.
    Tsatsanis, Christos
    Kampranis, Sotirios C.
    JOURNAL OF CELLULAR PHYSIOLOGY, 2018, 233 (09) : 6495 - 6507
  • [8] Epigenetic Modifications in Distinction: Histone versus DNA Methylation in ESCs
    Huang, Kevin
    Fan, Guoping
    CELL STEM CELL, 2011, 8 (06) : 604 - 605
  • [9] Epigenetic Therapy: Histone Acetylation, DNA Methylation and Anti-Cancer Drug Discovery
    Ganesan, A.
    Nolan, L.
    Crabb, S. J.
    Packham, G.
    CURRENT CANCER DRUG TARGETS, 2009, 9 (08) : 963 - 981
  • [10] Epigenetic Modification Related to Acetylation of Histone and Methylation of DNA as a Key Player in Immunological Disorders
    Qadir, Muhammad Imran
    Anwer, Farha
    CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, 2019, 29 (01): : 1 - 15