Isolation and characterization of the murine cardiotrophin-1 gene: Expression and norepinephrine-induced transcriptional activation

Masanobu Funamoto, Shigemichi Hishinuma, Yasushi Fujio, Yoichi Matsuda, Keita Kunisada, Hidemasa Oh, Shinji Negoro, Eiroh Tone, Tadamitsu Kishimoto, Keiko Yamauchi-Takihara

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Cardiotrophin-1 (CT-1) is a novel cytokine capable of inducing hypertrophy in cardiac myocytes and belongs to the interleukin-6 family that exert their biological effects through gp130. To clarify the involvement and pathophysiological role of CT-1 in myocardial diseases, it is important to characterize the regulation of CT-1 gene expression. In this study, we isolated and characterized the mouse CT-1 gene and studied the expression of CT-1 mRNA under norepinephrine (NE) stimulation. The mouse CT-1 gene constitutes 5.4 kilobases (kb) in length and consists of three exons and two introns. When nucleotide sequences of the coding regions of exons were compared with those of human, exon 1, 2 and 3 share 96%, 84% and 81% homology, respectively. The 2.2 kb of 5' flanking lesion of the mouse CT-1 gene contains a variety of transcription factor binding motif (e.g. CREB, MyoD. NF-IL6. Nkx2.5, GATA). Fluorescent in situ hybridization (FISH) analysis demonstrated that the mouse CT-1 gene was located on chromosome 7F3. The expression of CT-1 mRNA in cardiac myocytes was markedly augmented by NE stimulation, both in vivo and in vitro. Promoter analysis using deletion constructs of the CT-1 gene indicated that the NE responsive dement located between -2174/-1540 and this region contained the cAMP responsive element (CRE). Electrophoretic gel mobility shift assays showed enhanced binding activity to the CRE motif in the nuclear extracts from NE-stimulated cardiac myocytes. These studies indicate that CT-1 is abundantly expressed in the heart and that the CRE is a possible cis-acting dement of the CT-1 gene under NE-stimulation. These data suggest that the CT-1 gene expression is regulated, at least partially, by transcriptional machinery. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)1275-1284
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume32
Issue number7
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Transcriptional Activation
Norepinephrine
Gene Expression
Cardiac Myocytes
Exons
Genes
cardiotrophin 1
CCAAT-Enhancer-Binding Protein-beta
Messenger RNA
Electrophoretic Mobility Shift Assay
Fluorescence In Situ Hybridization
Cardiomyopathies
Introns
Hypertrophy
Interleukin-6
Transcription Factors
Chromosomes
Gels
Cytokines

Keywords

  • Chromosomal localization
  • Gene structure
  • Mouse cardiotrophin-1
  • Norepinephrine
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Isolation and characterization of the murine cardiotrophin-1 gene : Expression and norepinephrine-induced transcriptional activation. / Funamoto, Masanobu; Hishinuma, Shigemichi; Fujio, Yasushi; Matsuda, Yoichi; Kunisada, Keita; Oh, Hidemasa; Negoro, Shinji; Tone, Eiroh; Kishimoto, Tadamitsu; Yamauchi-Takihara, Keiko.

In: Journal of Molecular and Cellular Cardiology, Vol. 32, No. 7, 2000, p. 1275-1284.

Research output: Contribution to journalArticle

Funamoto, M, Hishinuma, S, Fujio, Y, Matsuda, Y, Kunisada, K, Oh, H, Negoro, S, Tone, E, Kishimoto, T & Yamauchi-Takihara, K 2000, 'Isolation and characterization of the murine cardiotrophin-1 gene: Expression and norepinephrine-induced transcriptional activation', Journal of Molecular and Cellular Cardiology, vol. 32, no. 7, pp. 1275-1284. https://doi.org/10.1006/jmcc.2000.1161
Funamoto, Masanobu ; Hishinuma, Shigemichi ; Fujio, Yasushi ; Matsuda, Yoichi ; Kunisada, Keita ; Oh, Hidemasa ; Negoro, Shinji ; Tone, Eiroh ; Kishimoto, Tadamitsu ; Yamauchi-Takihara, Keiko. / Isolation and characterization of the murine cardiotrophin-1 gene : Expression and norepinephrine-induced transcriptional activation. In: Journal of Molecular and Cellular Cardiology. 2000 ; Vol. 32, No. 7. pp. 1275-1284.
@article{9fa8806b0a6348369a410516f59441b3,
title = "Isolation and characterization of the murine cardiotrophin-1 gene: Expression and norepinephrine-induced transcriptional activation",
abstract = "Cardiotrophin-1 (CT-1) is a novel cytokine capable of inducing hypertrophy in cardiac myocytes and belongs to the interleukin-6 family that exert their biological effects through gp130. To clarify the involvement and pathophysiological role of CT-1 in myocardial diseases, it is important to characterize the regulation of CT-1 gene expression. In this study, we isolated and characterized the mouse CT-1 gene and studied the expression of CT-1 mRNA under norepinephrine (NE) stimulation. The mouse CT-1 gene constitutes 5.4 kilobases (kb) in length and consists of three exons and two introns. When nucleotide sequences of the coding regions of exons were compared with those of human, exon 1, 2 and 3 share 96{\%}, 84{\%} and 81{\%} homology, respectively. The 2.2 kb of 5' flanking lesion of the mouse CT-1 gene contains a variety of transcription factor binding motif (e.g. CREB, MyoD. NF-IL6. Nkx2.5, GATA). Fluorescent in situ hybridization (FISH) analysis demonstrated that the mouse CT-1 gene was located on chromosome 7F3. The expression of CT-1 mRNA in cardiac myocytes was markedly augmented by NE stimulation, both in vivo and in vitro. Promoter analysis using deletion constructs of the CT-1 gene indicated that the NE responsive dement located between -2174/-1540 and this region contained the cAMP responsive element (CRE). Electrophoretic gel mobility shift assays showed enhanced binding activity to the CRE motif in the nuclear extracts from NE-stimulated cardiac myocytes. These studies indicate that CT-1 is abundantly expressed in the heart and that the CRE is a possible cis-acting dement of the CT-1 gene under NE-stimulation. These data suggest that the CT-1 gene expression is regulated, at least partially, by transcriptional machinery. (C) 2000 Academic Press.",
keywords = "Chromosomal localization, Gene structure, Mouse cardiotrophin-1, Norepinephrine, Transcriptional regulation",
author = "Masanobu Funamoto and Shigemichi Hishinuma and Yasushi Fujio and Yoichi Matsuda and Keita Kunisada and Hidemasa Oh and Shinji Negoro and Eiroh Tone and Tadamitsu Kishimoto and Keiko Yamauchi-Takihara",
year = "2000",
doi = "10.1006/jmcc.2000.1161",
language = "English",
volume = "32",
pages = "1275--1284",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "7",

}

TY - JOUR

T1 - Isolation and characterization of the murine cardiotrophin-1 gene

T2 - Expression and norepinephrine-induced transcriptional activation

AU - Funamoto, Masanobu

AU - Hishinuma, Shigemichi

AU - Fujio, Yasushi

AU - Matsuda, Yoichi

AU - Kunisada, Keita

AU - Oh, Hidemasa

AU - Negoro, Shinji

AU - Tone, Eiroh

AU - Kishimoto, Tadamitsu

AU - Yamauchi-Takihara, Keiko

PY - 2000

Y1 - 2000

N2 - Cardiotrophin-1 (CT-1) is a novel cytokine capable of inducing hypertrophy in cardiac myocytes and belongs to the interleukin-6 family that exert their biological effects through gp130. To clarify the involvement and pathophysiological role of CT-1 in myocardial diseases, it is important to characterize the regulation of CT-1 gene expression. In this study, we isolated and characterized the mouse CT-1 gene and studied the expression of CT-1 mRNA under norepinephrine (NE) stimulation. The mouse CT-1 gene constitutes 5.4 kilobases (kb) in length and consists of three exons and two introns. When nucleotide sequences of the coding regions of exons were compared with those of human, exon 1, 2 and 3 share 96%, 84% and 81% homology, respectively. The 2.2 kb of 5' flanking lesion of the mouse CT-1 gene contains a variety of transcription factor binding motif (e.g. CREB, MyoD. NF-IL6. Nkx2.5, GATA). Fluorescent in situ hybridization (FISH) analysis demonstrated that the mouse CT-1 gene was located on chromosome 7F3. The expression of CT-1 mRNA in cardiac myocytes was markedly augmented by NE stimulation, both in vivo and in vitro. Promoter analysis using deletion constructs of the CT-1 gene indicated that the NE responsive dement located between -2174/-1540 and this region contained the cAMP responsive element (CRE). Electrophoretic gel mobility shift assays showed enhanced binding activity to the CRE motif in the nuclear extracts from NE-stimulated cardiac myocytes. These studies indicate that CT-1 is abundantly expressed in the heart and that the CRE is a possible cis-acting dement of the CT-1 gene under NE-stimulation. These data suggest that the CT-1 gene expression is regulated, at least partially, by transcriptional machinery. (C) 2000 Academic Press.

AB - Cardiotrophin-1 (CT-1) is a novel cytokine capable of inducing hypertrophy in cardiac myocytes and belongs to the interleukin-6 family that exert their biological effects through gp130. To clarify the involvement and pathophysiological role of CT-1 in myocardial diseases, it is important to characterize the regulation of CT-1 gene expression. In this study, we isolated and characterized the mouse CT-1 gene and studied the expression of CT-1 mRNA under norepinephrine (NE) stimulation. The mouse CT-1 gene constitutes 5.4 kilobases (kb) in length and consists of three exons and two introns. When nucleotide sequences of the coding regions of exons were compared with those of human, exon 1, 2 and 3 share 96%, 84% and 81% homology, respectively. The 2.2 kb of 5' flanking lesion of the mouse CT-1 gene contains a variety of transcription factor binding motif (e.g. CREB, MyoD. NF-IL6. Nkx2.5, GATA). Fluorescent in situ hybridization (FISH) analysis demonstrated that the mouse CT-1 gene was located on chromosome 7F3. The expression of CT-1 mRNA in cardiac myocytes was markedly augmented by NE stimulation, both in vivo and in vitro. Promoter analysis using deletion constructs of the CT-1 gene indicated that the NE responsive dement located between -2174/-1540 and this region contained the cAMP responsive element (CRE). Electrophoretic gel mobility shift assays showed enhanced binding activity to the CRE motif in the nuclear extracts from NE-stimulated cardiac myocytes. These studies indicate that CT-1 is abundantly expressed in the heart and that the CRE is a possible cis-acting dement of the CT-1 gene under NE-stimulation. These data suggest that the CT-1 gene expression is regulated, at least partially, by transcriptional machinery. (C) 2000 Academic Press.

KW - Chromosomal localization

KW - Gene structure

KW - Mouse cardiotrophin-1

KW - Norepinephrine

KW - Transcriptional regulation

UR - http://www.scopus.com/inward/record.url?scp=0033843970&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033843970&partnerID=8YFLogxK

U2 - 10.1006/jmcc.2000.1161

DO - 10.1006/jmcc.2000.1161

M3 - Article

C2 - 10860769

AN - SCOPUS:0033843970

VL - 32

SP - 1275

EP - 1284

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 7

ER -