Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes.

Amin JK, Xiao L, Pimental DR, Pagano PJ, Singh K, Sawyer DB, Colucci WS
J Mol Cell Cardiol. 2001 33 (1): 131-9

PMID: 11133229 · DOI:10.1006/jmcc.2000.1285

Norepinephrine (NE) causes hypertrophic growth of cardiac myocytes via stimulation of alpha1-adrenergic receptors (alpha1-AR). Reactive oxygen species (ROS) can act as signaling molecules for cell growth. Accordingly, we tested the hypothesis that ROS mediate alpha1-AR-stimulated hypertrophic growth in adult rat ventricular myocytes (ARVM). NE increased the level of intracellular ROS as assessed by lucigenin chemiluminescence or cytochrome c reduction, and this effect was prevented by the superoxide dismutase (SOD)-mimetic MnTMPyP. NE also caused the induction of MnSOD mRNA. alpha1-AR stimulation with NE (1 microM) in the presence of propranolol (2 microM) for 48-96 h caused a hypertrophic growth phenotype characterized by a 36+/-3% increase in 3H-leucine incorporation, a 49+/-14% increase in protein accumulation, a six-fold induction of atrial natriuretic peptide mRNA, actin filament reorganization, and the induction of MnSOD mRNA. These responses were all prevented by pretreatment with the alpha1-AR-selective antagonist prazosin (100 n M) or the SOD-mimetics MnTMPyP (50 microM) and Euk-8 (100 microM). MnTMPyP had no effect on alpha1-AR-stimulated 3H-inositol phosphate turnover or the hypertrophic phenotype caused by the protein kinase C activator phorbol-12-myristate-13-acetate. Thus, ROS play a critical role in mediating the hypertrophic growth response to alpha1-AR-stimulation in ARVM.

MeSH Terms (23)

Actin Cytoskeleton Actins Animals Atrial Natriuretic Factor Cell Division Enzyme Induction Ethylenediamines Gene Expression Regulation Heart Heart Ventricles Hypertrophy Inositol Phosphates Myocardium Norepinephrine Organometallic Compounds Porphyrins Prazosin Rats Reactive Oxygen Species Receptors, Adrenergic, alpha-1 RNA, Messenger Signal Transduction Superoxide Dismutase

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