Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro:: activation of CREB downstream of GSK3β

被引:53
作者
El Jamali, A
Freund, C
Rechner, C
Scheidereit, C
Dietz, R
Bergmann, MW
机构
[1] HELIOS Klin, Franz Volhard Clin, Berlin, Germany
[2] Max Delbruck Ctr Mol Med, Berlin, Germany
关键词
cardiac hypertrophy; heart failure; CRE-dependent transcription;
D O I
10.1096/fj.03-1054fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vivo, left ventricular remodeling after myocardial infarction involves hypertrophy generally attributed to increased cardiac workload. We hypothesized that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied several participating kinases and transcription factors in isolated cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced cardiomyocyte hypertrophy assessed by H-3 leucine incorporation and immunohistochemistry. Inhibition of reactive oxygen species (ROS), serine/threonine kinase AKT, and ERK abolished reoxygenation-induced hypertrophy. In addition, a beta2-adrenergic receptor (beta2-AR) antagonist, as well as Gi inhibitor pertussis toxin, blocked reoxygenation- induced hypertrophy. Hypoxia for 6 h increased transcription factors CREB, NF-kappaB, and GATA DNA binding activities. However, only CREB DNA-binding was sustained during reoxygenation. Inhibition of PI3-kinase, ERK, and PKA abrogated reoxygenation- induced CREB DNA-binding without affecting CREB serine-133 phosphorylation. These same pathways were found to regulate hypoxia/reoxygenation-induced GSK3beta kinase activity and CREB serine-129 de-phosphorylation. GSK3beta mutants resistant to phosphorylation blocked the stimulation of CRE-dependent transcription induced by hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant-negative mutant of CREB abrogated hypoxia/reoxygenation-induced hypertrophy. We suggest that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB activation. Inactivation of GSK3beta by hypoxia/reoxygenation, possibly integrating PI3-kinase and ERK pathways downstream of beta2-AR and ROS, is a prerequisite for CRE-dependent transcription. Transient hypoxia may contribute to cardiac hypertrophy in ischemic heart disease independent of cardiac workload.
引用
收藏
页码:1096 / +
页数:24
相关论文
共 49 条
  • [21] Critical role of cAMP-response element-binding protein for angiotensin II-induced hypertrophy of vascular smooth muscle cells
    Funakoshi, Y
    Ichiki, T
    Takeda, H
    Tokuno, T
    Iino, N
    Takeshita, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (21) : 18710 - 18717
  • [22] PHYSIOLOGICAL-MECHANISMS OF POSTISCHEMIC TISSUE-INJURY
    GRANGER, DN
    KORTHUIS, RJ
    [J]. ANNUAL REVIEW OF PHYSIOLOGY, 1995, 57 : 311 - 332
  • [23] CREB DNA binding activity is inhibited by glycogen synthase kinase-3β and facilitated by lithium
    Grimes, CA
    Jope, RS
    [J]. JOURNAL OF NEUROCHEMISTRY, 2001, 78 (06) : 1219 - 1232
  • [24] Stabilization of β-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth
    Haq, S
    Michael, A
    Andreucci, M
    Bhattacharya, K
    Dotto, P
    Walters, B
    Woodgett, J
    Kilter, H
    Force, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) : 4610 - 4615
  • [25] Involvement of nuclear factor-κB and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy
    Hirotani, S
    Otsu, K
    Nishida, K
    Higuchi, Y
    Morita, T
    Nakayama, H
    Yamaguchi, O
    Mano, T
    Matsumura, Y
    Ueno, H
    Tada, M
    Hori, M
    [J]. CIRCULATION, 2002, 105 (04) : 509 - 515
  • [26] Hypoxia-inducible factor and its biomedical relevance
    Huang, LE
    Bunn, HF
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (22) : 19575 - 19578
  • [27] TYPE-I ADENYLYL-CYCLASE FUNCTIONS AS A COINCIDENCE DETECTOR FOR CONTROL OF CYCLIC-AMP RESPONSE ELEMENT-MEDIATED TRANSCRIPTION - SYNERGISTIC REGULATION OF TRANSCRIPTION BY CA2+ AND ISOPROTERENOL
    IMPEY, S
    WAYMAN, G
    WU, ZL
    STORM, DR
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (12) : 8272 - 8281
  • [28] Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation
    Impey, S
    Obrietan, K
    Wong, ST
    Poser, S
    Yano, S
    Wayman, G
    Deloulme, JC
    Chan, G
    Storm, DR
    [J]. NEURON, 1998, 21 (04) : 869 - 883
  • [29] Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation
    Kang, PM
    Haunstetter, A
    Aoki, H
    Usheva, A
    Izumo, S
    [J]. CIRCULATION RESEARCH, 2000, 87 (02) : 118 - 125
  • [30] Platelet-derived growth factor activates production of reactive oxygen species by NAD(P)H-oxidase in smooth muscle cells through Gi1,2
    Kreuzer, J
    Viedt, C
    Brandes, RP
    Seeger, F
    Rosenkranz, AS
    Sauer, H
    Babich, A
    Nürnberg, B
    Kather, H
    Krieger-Brauer, HI
    [J]. FASEB JOURNAL, 2002, 16 (13) : 38 - +