Epigenetic regulation of cardiac muscle-specific genes in H9c2 cells by Interleukin-18 and histone deacetylase inhibitor m -carboxycinnamic acid bis -hydroxamide

Gipsy Majumdar, I. Maria Johnson, Santosh Kale, Rajendra Raghow

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Interleukin-18 (IL-18) elicited a robust hypertrophy response in H9c2 cardiomyocytes as judged by their accelerated rates of protein synthesis and increased cell size. Evidently, IL-18 treatment also induced a cardiac hypertrophy-specific program of gene expression in H9c2 cardiomyocytes since they elicited enhanced expression of atrial naturetic factor (ANF), desmin, and skeletal α-actin genes accompanied by a canonical switch in the transcription of α- and β-myosin heavy chain (MyHC) genes. Co-treatment of H9c2 cells with m-carboxycinnamic acid bis-hydroxamide (CBHA), an inhibitor of histone deacetylases, significantly blocked both morphological and molecular manifestations of IL-18-induced cardiac hypertrophy in vitro. IL-18 treatment led to activation of phosphoinositide-3-kinase and phosphorylated Akt/protein kinase B, while CBHA blunted this pathway via inducing the expression of its upstream regulator, PTEN (phosphatase and tensin homolog). The architecture of bulk chromatin of H9c2 cells exposed to IL-18 and/or CBHA was significantly altered as judged by the extent of covalent modifications of its constituent histones. The chromatin immuno-precipitation (ChIP) assays revealed that IL-18-induced specific epigenetic changes in the chromatin of ANF, desmin, skeletal α-actin, and MyHC genes that were largely neutralized by CBHA. We demonstrate for the first time that 'histone code' of the entire ∼50 kb genomic DNA encoding the α- and β-MyHC genes and the intergenic DNA that generates anti-β-MyHC RNA was uniquely modulated by pro- and anti-hypertrophy signals of IL-18 and CBHA, respectively.

Original languageEnglish (US)
Pages (from-to)47-60
Number of pages14
JournalMolecular and Cellular Biochemistry
Volume312
Issue number1-2
DOIs
StatePublished - May 1 2008

Fingerprint

Interleukin-18
Histone Deacetylase Inhibitors
Epigenomics
Muscle
Myocardium
Genes
Myosin Heavy Chains
Acids
Hypertrophy
Chromatin
Desmin
Cardiomegaly
Cardiac Myocytes
Histones
Actins
Histone Code
Proto-Oncogene Proteins c-akt
Intergenic DNA
Histone Deacetylases
1-Phosphatidylinositol 4-Kinase

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Epigenetic regulation of cardiac muscle-specific genes in H9c2 cells by Interleukin-18 and histone deacetylase inhibitor m -carboxycinnamic acid bis -hydroxamide. / Majumdar, Gipsy; Johnson, I. Maria; Kale, Santosh; Raghow, Rajendra.

In: Molecular and Cellular Biochemistry, Vol. 312, No. 1-2, 01.05.2008, p. 47-60.

Research output: Contribution to journalArticle

@article{6f501afa11794ecbacd59e89d7e22bfb,
title = "Epigenetic regulation of cardiac muscle-specific genes in H9c2 cells by Interleukin-18 and histone deacetylase inhibitor m -carboxycinnamic acid bis -hydroxamide",
abstract = "Interleukin-18 (IL-18) elicited a robust hypertrophy response in H9c2 cardiomyocytes as judged by their accelerated rates of protein synthesis and increased cell size. Evidently, IL-18 treatment also induced a cardiac hypertrophy-specific program of gene expression in H9c2 cardiomyocytes since they elicited enhanced expression of atrial naturetic factor (ANF), desmin, and skeletal α-actin genes accompanied by a canonical switch in the transcription of α- and β-myosin heavy chain (MyHC) genes. Co-treatment of H9c2 cells with m-carboxycinnamic acid bis-hydroxamide (CBHA), an inhibitor of histone deacetylases, significantly blocked both morphological and molecular manifestations of IL-18-induced cardiac hypertrophy in vitro. IL-18 treatment led to activation of phosphoinositide-3-kinase and phosphorylated Akt/protein kinase B, while CBHA blunted this pathway via inducing the expression of its upstream regulator, PTEN (phosphatase and tensin homolog). The architecture of bulk chromatin of H9c2 cells exposed to IL-18 and/or CBHA was significantly altered as judged by the extent of covalent modifications of its constituent histones. The chromatin immuno-precipitation (ChIP) assays revealed that IL-18-induced specific epigenetic changes in the chromatin of ANF, desmin, skeletal α-actin, and MyHC genes that were largely neutralized by CBHA. We demonstrate for the first time that 'histone code' of the entire ∼50 kb genomic DNA encoding the α- and β-MyHC genes and the intergenic DNA that generates anti-β-MyHC RNA was uniquely modulated by pro- and anti-hypertrophy signals of IL-18 and CBHA, respectively.",
author = "Gipsy Majumdar and Johnson, {I. Maria} and Santosh Kale and Rajendra Raghow",
year = "2008",
month = "5",
day = "1",
doi = "10.1007/s11010-008-9720-x",
language = "English (US)",
volume = "312",
pages = "47--60",
journal = "Molecular and Cellular Biochemistry",
issn = "0300-8177",
publisher = "Springer Netherlands",
number = "1-2",

}

TY - JOUR

T1 - Epigenetic regulation of cardiac muscle-specific genes in H9c2 cells by Interleukin-18 and histone deacetylase inhibitor m -carboxycinnamic acid bis -hydroxamide

AU - Majumdar, Gipsy

AU - Johnson, I. Maria

AU - Kale, Santosh

AU - Raghow, Rajendra

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Interleukin-18 (IL-18) elicited a robust hypertrophy response in H9c2 cardiomyocytes as judged by their accelerated rates of protein synthesis and increased cell size. Evidently, IL-18 treatment also induced a cardiac hypertrophy-specific program of gene expression in H9c2 cardiomyocytes since they elicited enhanced expression of atrial naturetic factor (ANF), desmin, and skeletal α-actin genes accompanied by a canonical switch in the transcription of α- and β-myosin heavy chain (MyHC) genes. Co-treatment of H9c2 cells with m-carboxycinnamic acid bis-hydroxamide (CBHA), an inhibitor of histone deacetylases, significantly blocked both morphological and molecular manifestations of IL-18-induced cardiac hypertrophy in vitro. IL-18 treatment led to activation of phosphoinositide-3-kinase and phosphorylated Akt/protein kinase B, while CBHA blunted this pathway via inducing the expression of its upstream regulator, PTEN (phosphatase and tensin homolog). The architecture of bulk chromatin of H9c2 cells exposed to IL-18 and/or CBHA was significantly altered as judged by the extent of covalent modifications of its constituent histones. The chromatin immuno-precipitation (ChIP) assays revealed that IL-18-induced specific epigenetic changes in the chromatin of ANF, desmin, skeletal α-actin, and MyHC genes that were largely neutralized by CBHA. We demonstrate for the first time that 'histone code' of the entire ∼50 kb genomic DNA encoding the α- and β-MyHC genes and the intergenic DNA that generates anti-β-MyHC RNA was uniquely modulated by pro- and anti-hypertrophy signals of IL-18 and CBHA, respectively.

AB - Interleukin-18 (IL-18) elicited a robust hypertrophy response in H9c2 cardiomyocytes as judged by their accelerated rates of protein synthesis and increased cell size. Evidently, IL-18 treatment also induced a cardiac hypertrophy-specific program of gene expression in H9c2 cardiomyocytes since they elicited enhanced expression of atrial naturetic factor (ANF), desmin, and skeletal α-actin genes accompanied by a canonical switch in the transcription of α- and β-myosin heavy chain (MyHC) genes. Co-treatment of H9c2 cells with m-carboxycinnamic acid bis-hydroxamide (CBHA), an inhibitor of histone deacetylases, significantly blocked both morphological and molecular manifestations of IL-18-induced cardiac hypertrophy in vitro. IL-18 treatment led to activation of phosphoinositide-3-kinase and phosphorylated Akt/protein kinase B, while CBHA blunted this pathway via inducing the expression of its upstream regulator, PTEN (phosphatase and tensin homolog). The architecture of bulk chromatin of H9c2 cells exposed to IL-18 and/or CBHA was significantly altered as judged by the extent of covalent modifications of its constituent histones. The chromatin immuno-precipitation (ChIP) assays revealed that IL-18-induced specific epigenetic changes in the chromatin of ANF, desmin, skeletal α-actin, and MyHC genes that were largely neutralized by CBHA. We demonstrate for the first time that 'histone code' of the entire ∼50 kb genomic DNA encoding the α- and β-MyHC genes and the intergenic DNA that generates anti-β-MyHC RNA was uniquely modulated by pro- and anti-hypertrophy signals of IL-18 and CBHA, respectively.

UR - http://www.scopus.com/inward/record.url?scp=42149139641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42149139641&partnerID=8YFLogxK

U2 - 10.1007/s11010-008-9720-x

DO - 10.1007/s11010-008-9720-x

M3 - Article

C2 - 18292970

AN - SCOPUS:42149139641

VL - 312

SP - 47

EP - 60

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

IS - 1-2

ER -