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 language | English |
|---|---|
| Pages (from-to) | 1275-1284 |
| Number of pages | 10 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 32 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2000 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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 -