Angiotensin II potentiates DNA synthesis in AT-1 transformed cardiomyocytes

Keiichi Fukuda, Seigo Izumo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Angiotensin II has been shown to be mitogenic in various cell types. In cultured neonatal cardiomyocytes, we have demonstrated that angiotensin II causes hypertrophy, not hyperplasia. However, fetal or neonatal cardiomyocytes exhibit limited proliferation in primary culture, and are mitotically less potent. In order to determine whether angiotensin II is simply a hypertrophic or hyperplastic growth factor for mitotically-potent cardiomyocytes, we analysed [3H]-thymidine uptake and cell cycle-regulated gene expression using SV40 large T-transformed AT-1 cardiomyocytes. Angiotensin II, alone and in combination with other growth factors, increased [3H]-thymidine uptake in a dose-dependent manner. The mRNA expression of G1 cyclins (Cyclin C, D1, D2, D3) and histone H1-kinase activity by CDK2 increased 6 h after angiotensin II stimulation. Western blot analysis revealed cyclin B1 expression after 18 h, which peaked at 30 h. Histone H1-kinase activity by cdc2 was also increased by angiotensin II, and peaked at 24-36 h, indicating that these changes were cell cycle dependent. Double immunofluorescent photography showed that AT-1 cells incorporated BrdU, and expressed cdc2 by angiotensin II stimulation. [3H]-thymidine and BrdU uptake were blocked by losartan, but not by PD123319. In contrast with neonatal cardiomyocytes, angiotensin II potentiated DNA synthesis and induced cell cycle regulated gene expression in AT-1 cardiomyocytes, and this activity was mediated by the angiotensin II type-1 receptor.

Original languageEnglish
Pages (from-to)2069-2080
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number10
DOIs
Publication statusPublished - 1998 Oct

Fingerprint

Cardiac Myocytes
Angiotensin II
DNA
Thymidine
cdc Genes
Bromodeoxyuridine
Cyclin C
Intercellular Signaling Peptides and Proteins
Cyclin G1
Cyclin B1
Gene Expression
Angiotensin Type 1 Receptor
Losartan
Photography
Cyclin D1
Hypertrophy
Hyperplasia
Cell Cycle
Western Blotting
Messenger RNA

Keywords

  • Angiotensin II
  • AT-1 cardiomyocyte
  • Cardiac hypertrophy
  • Cyclin
  • Hyperplasia
  • Mitogenesity

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Angiotensin II potentiates DNA synthesis in AT-1 transformed cardiomyocytes. / Fukuda, Keiichi; Izumo, Seigo.

In: Journal of Molecular and Cellular Cardiology, Vol. 30, No. 10, 10.1998, p. 2069-2080.

Research output: Contribution to journalArticle

@article{d653f39382bc428faa78db0462f25281,
title = "Angiotensin II potentiates DNA synthesis in AT-1 transformed cardiomyocytes",
abstract = "Angiotensin II has been shown to be mitogenic in various cell types. In cultured neonatal cardiomyocytes, we have demonstrated that angiotensin II causes hypertrophy, not hyperplasia. However, fetal or neonatal cardiomyocytes exhibit limited proliferation in primary culture, and are mitotically less potent. In order to determine whether angiotensin II is simply a hypertrophic or hyperplastic growth factor for mitotically-potent cardiomyocytes, we analysed [3H]-thymidine uptake and cell cycle-regulated gene expression using SV40 large T-transformed AT-1 cardiomyocytes. Angiotensin II, alone and in combination with other growth factors, increased [3H]-thymidine uptake in a dose-dependent manner. The mRNA expression of G1 cyclins (Cyclin C, D1, D2, D3) and histone H1-kinase activity by CDK2 increased 6 h after angiotensin II stimulation. Western blot analysis revealed cyclin B1 expression after 18 h, which peaked at 30 h. Histone H1-kinase activity by cdc2 was also increased by angiotensin II, and peaked at 24-36 h, indicating that these changes were cell cycle dependent. Double immunofluorescent photography showed that AT-1 cells incorporated BrdU, and expressed cdc2 by angiotensin II stimulation. [3H]-thymidine and BrdU uptake were blocked by losartan, but not by PD123319. In contrast with neonatal cardiomyocytes, angiotensin II potentiated DNA synthesis and induced cell cycle regulated gene expression in AT-1 cardiomyocytes, and this activity was mediated by the angiotensin II type-1 receptor.",
keywords = "Angiotensin II, AT-1 cardiomyocyte, Cardiac hypertrophy, Cyclin, Hyperplasia, Mitogenesity",
author = "Keiichi Fukuda and Seigo Izumo",
year = "1998",
month = "10",
doi = "10.1006/jmcc.1998.0770",
language = "English",
volume = "30",
pages = "2069--2080",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "10",

}

TY - JOUR

T1 - Angiotensin II potentiates DNA synthesis in AT-1 transformed cardiomyocytes

AU - Fukuda, Keiichi

AU - Izumo, Seigo

PY - 1998/10

Y1 - 1998/10

N2 - Angiotensin II has been shown to be mitogenic in various cell types. In cultured neonatal cardiomyocytes, we have demonstrated that angiotensin II causes hypertrophy, not hyperplasia. However, fetal or neonatal cardiomyocytes exhibit limited proliferation in primary culture, and are mitotically less potent. In order to determine whether angiotensin II is simply a hypertrophic or hyperplastic growth factor for mitotically-potent cardiomyocytes, we analysed [3H]-thymidine uptake and cell cycle-regulated gene expression using SV40 large T-transformed AT-1 cardiomyocytes. Angiotensin II, alone and in combination with other growth factors, increased [3H]-thymidine uptake in a dose-dependent manner. The mRNA expression of G1 cyclins (Cyclin C, D1, D2, D3) and histone H1-kinase activity by CDK2 increased 6 h after angiotensin II stimulation. Western blot analysis revealed cyclin B1 expression after 18 h, which peaked at 30 h. Histone H1-kinase activity by cdc2 was also increased by angiotensin II, and peaked at 24-36 h, indicating that these changes were cell cycle dependent. Double immunofluorescent photography showed that AT-1 cells incorporated BrdU, and expressed cdc2 by angiotensin II stimulation. [3H]-thymidine and BrdU uptake were blocked by losartan, but not by PD123319. In contrast with neonatal cardiomyocytes, angiotensin II potentiated DNA synthesis and induced cell cycle regulated gene expression in AT-1 cardiomyocytes, and this activity was mediated by the angiotensin II type-1 receptor.

AB - Angiotensin II has been shown to be mitogenic in various cell types. In cultured neonatal cardiomyocytes, we have demonstrated that angiotensin II causes hypertrophy, not hyperplasia. However, fetal or neonatal cardiomyocytes exhibit limited proliferation in primary culture, and are mitotically less potent. In order to determine whether angiotensin II is simply a hypertrophic or hyperplastic growth factor for mitotically-potent cardiomyocytes, we analysed [3H]-thymidine uptake and cell cycle-regulated gene expression using SV40 large T-transformed AT-1 cardiomyocytes. Angiotensin II, alone and in combination with other growth factors, increased [3H]-thymidine uptake in a dose-dependent manner. The mRNA expression of G1 cyclins (Cyclin C, D1, D2, D3) and histone H1-kinase activity by CDK2 increased 6 h after angiotensin II stimulation. Western blot analysis revealed cyclin B1 expression after 18 h, which peaked at 30 h. Histone H1-kinase activity by cdc2 was also increased by angiotensin II, and peaked at 24-36 h, indicating that these changes were cell cycle dependent. Double immunofluorescent photography showed that AT-1 cells incorporated BrdU, and expressed cdc2 by angiotensin II stimulation. [3H]-thymidine and BrdU uptake were blocked by losartan, but not by PD123319. In contrast with neonatal cardiomyocytes, angiotensin II potentiated DNA synthesis and induced cell cycle regulated gene expression in AT-1 cardiomyocytes, and this activity was mediated by the angiotensin II type-1 receptor.

KW - Angiotensin II

KW - AT-1 cardiomyocyte

KW - Cardiac hypertrophy

KW - Cyclin

KW - Hyperplasia

KW - Mitogenesity

UR - http://www.scopus.com/inward/record.url?scp=0032191705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032191705&partnerID=8YFLogxK

U2 - 10.1006/jmcc.1998.0770

DO - 10.1006/jmcc.1998.0770

M3 - Article

C2 - 9799660

AN - SCOPUS:0032191705

VL - 30

SP - 2069

EP - 2080

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 10

ER -