Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in vitro

被引:68
作者
Busk, PK
Bartkova, J
Strom, CC
Wulf-Andersen, L
Hinrichsen, R
Christoffersen, TEH
Latella, L
Bartek, J
Haunso, S
Sheikh, SP
机构
[1] Rigshosp, Lab Mol Kardiol, DK-2100 Copenhagen O, Denmark
[2] Rigshosp, Hjertecenteret HS, DK-2100 Copenhagen O, Denmark
[3] Danish Canc Soc, Dept Cell Cycle & Canc, DK-2100 Copenhagen O, Denmark
关键词
hypertrophy; myocytes; signal transduction; gene expression; protein kinases;
D O I
10.1016/S0008-6363(02)00510-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Cardiac hypertrophy is induced by a number of stimuli and can lead to cardiomyopathy and heart failure. Present knowledge suggests that cell-cycle regulatory proteins take part in hypertrophy. We have investigated if the D-type cyclins are involved in cardiac hypertrophy. Methods: The expression and activity of the D-type cyclins and associated kinases in cardiomyocytes were studied during angiotensin II- and pressure overload-induced hypertrophy in rats (Rattus norvegicus) and in isolated, neonatal cardiomyocytes. Expression of the D-type cyclins was manipulated pharmacologically and genetically in neonatal myocytes. Results: In the left ventricle, there was a low, constitutive expression of the D-type cyclins, which may have a biological role in normal, adult myocytes. The protein level and the associated kinase activity of the D-type cyclins were up-regulated during hypertrophic growth. The increase in cyclin D expression could be mimicked in vitro in neonatal cardiac myocytes. Interestingly, the cyclin Ds were up-regulated by hypertrophic elicitors that stimulate different signalling pathways, suggesting that cyclin D expression is an inherent part of cardiac hypertrophy. Treatment of myocytes with the compound differentiation inducing factor I inhibited expression of the D-type cyclins and impaired hypertrophic growth induced by angiotensin 11, phenylephrine and serum. The response to hypertrophic elicitors could be restored in differentiation inducing factor 1-treated myocytes by expressing cyclin D2 from a heterologous promoter. Conclusion: Our results point to the D-type cyclins as important regulators of cardiac hypertrophy. This supports the notion that cell-cycle regulatory proteins regulate hypertrophic growth. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:64 / 75
页数:12
相关论文
共 53 条
  • [31] RETINOBLASTOMA-PROTEIN-DEPENDENT CELL-CYCLE INHIBITION BY THE TUMOR-SUPPRESSOR P16
    LUKAS, J
    PARRY, D
    AAGAARD, L
    MANN, DJ
    BARTKOVA, J
    STRAUSS, M
    PETERS, G
    BARTEK, J
    [J]. NATURE, 1995, 375 (6531) : 503 - 506
  • [32] The puc1 cyclin regulates the G1 phase of the fission yeast cell cycle in response to cell size
    Martín-Castellanos, C
    Blanco, MA
    de Prada, JM
    Moreno, S
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (02) : 543 - 554
  • [33] Differentiation-inducing factor-1, a morphogen of Dictyostelium, induces G1 arrest and differentiation of vascular smooth muscle cells
    Miwa, Y
    Sasaguri, T
    Kosaka, C
    Taba, Y
    Ishida, A
    Abumiya, T
    Kubohara, Y
    [J]. CIRCULATION RESEARCH, 2000, 86 (01) : 68 - 75
  • [34] A calcineurin-dependent transcriptional pathway for cardiac hypertrophy
    Molkentin, JD
    Lu, JR
    Antos, CL
    Markham, B
    Richardson, J
    Robbins, J
    Grant, SR
    Olson, EN
    [J]. CELL, 1998, 93 (02) : 215 - 228
  • [35] Calcineurin and beyond - Cardiac hypertrophic signaling
    Molkentin, JD
    [J]. CIRCULATION RESEARCH, 2000, 87 (09) : 731 - 738
  • [36] Accumulation of high levels of the p53 and p130 growth-suppressing proteins in cell lines stably over-expressing cyclin-dependent kinase 6 (cdk6)
    Nagasawa, M
    Gelfand, EW
    Lucas, JJ
    [J]. ONCOGENE, 2001, 20 (23) : 2889 - 2899
  • [37] G1 cyclins are involved in the mechanism of cardiac myocyte hypertrophy induced by angiotensin II
    Nozato, T
    Ito, H
    Tamamori, M
    Adachi, S
    Abe, S
    Marumo, F
    Hiroe, M
    [J]. JAPANESE CIRCULATION JOURNAL-ENGLISH EDITION, 2000, 64 (08): : 595 - 601
  • [38] Overexpression of cdk inhibitor p16INK4a by adenovirus vector inhibits cardiac hypertrophy in vitro and in vivo:: a novel strategy for the gene therapy of cardiac hypertrophy
    Nozato, T
    Ito, H
    Watanabe, M
    Ono, Y
    Adachi, S
    Tanaka, H
    Hiroe, M
    Sunamori, M
    Marumo, F
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2001, 33 (08) : 1493 - 1504
  • [39] OHTSUBO M, 1995, MOL CELL BIOL, V15, P2612
  • [40] CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo
    Passier, R
    Zeng, H
    Frey, N
    Naya, FJ
    Nicol, RL
    McKinsey, TA
    Overbeek, P
    Richardson, JA
    Grant, SR
    Olson, EN
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (10) : 1395 - 1406