PMID- 24495916
OWN - NLM
STAT- MEDLINE
DCOM- 20141228
LR  - 20211109
IS  - 1531-2267 (Electronic)
IS  - 1094-8341 (Print)
IS  - 1094-8341 (Linking)
VI  - 46
IP  - 7
DP  - 2014 Apr 1
TI  - Differential regulation of DNA methylation versus histone acetylation in 
      cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism.
PG  - 245-55
LID - 10.1152/physiolgenomics.00168.2013 [doi]
AB  - 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 muM homocysteine 
      in a dose-dependent manner. NMDAR1 antagonist (MK801) was added in the absence 
      and presence of homocysteine at 10 muM 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. Hyperhomocysteinemic 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.
FAU - Chaturvedi, Pankaj
AU  - Chaturvedi P
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, Kentucky.
FAU - Kalani, Anuradha
AU  - Kalani A
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Kamat, Pradip Kumar
AU  - Kamat PK
FAU - Familtseva, Anastasia
AU  - Familtseva A
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-108621/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140204
PL  - United States
TA  - Physiol Genomics
JT  - Physiological genomics
JID - 9815683
RN  - 0 (Histones)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - *DNA Methylation
MH  - *Epigenesis, Genetic
MH  - *Histones
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/metabolism
MH  - Myocytes, Cardiac/*metabolism
MH  - Oxidative Stress
PMC - PMC4035660
OTO - NOTNLM
OT  - DNA methylation
OT  - cardiomyocytes
OT  - histone modification
OT  - hyperhomocysteinemia
OT  - microRNA
EDAT- 2014/02/06 06:00
MHDA- 2014/12/30 06:00
PMCR- 2015/04/01
CRDT- 2014/02/06 06:00
PHST- 2014/02/06 06:00 [entrez]
PHST- 2014/02/06 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - physiolgenomics.00168.2013 [pii]
AID - PG-00168-2013 [pii]
AID - 10.1152/physiolgenomics.00168.2013 [doi]
PST - ppublish
SO  - Physiol Genomics. 2014 Apr 1;46(7):245-55. doi: 
      10.1152/physiolgenomics.00168.2013. Epub 2014 Feb 4.