Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes
Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes
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DOI：
10.1006/jmcc.2000.1285
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发表时间：
2001-01-01
影响因子：
5
通讯作者：
Colucci, WS
中科院分区：
文献类型：
--
作者：
Amin, JK;Xiao, L;Colucci, WS
去甲肾上腺素（NE）通过刺激α（1）-肾上腺素能受体（α（1）-AR）引起心肌细胞肥大性生长。活性氧（ROS）可以作为细胞生长的信号分子。因此，我们验证了ROS介导α（1）-AR刺激的成年大鼠心室肌细胞（ARVM）肥大生长的假设。NE增加细胞内ROS的水平，光泽精化学发光或细胞色素c还原评估，这种影响被阻止的超氧化物歧化酶（SOD）模拟MnTMPyP。NE还可诱导MnSOD mRNA的表达。在普萘洛尔（2 μ M）存在下，用NE（1 μ M）刺激α（1）-AR 48-96小时，引起肥大生长表型，其特征为H-3-亮氨酸掺入增加36 +/- 3%，蛋白质积累增加49 +/- 14%，心房钠尿肽mRNA诱导增加6倍，肌动蛋白丝重组和MnSOD mRNA诱导。这些反应都被预先用α（1）-AR-选择性拮抗剂哌唑嗪（100 nM）或SOD-模拟物MnTMPyP（50 μ M）和Euk-8（100 μ M）预防。MnTMPyP对α（1）-AR刺激的H-3-磷酸肌醇周转或蛋白激酶C激活剂佛波醇-12-肉豆蔻酸酯-13-乙酸酯引起的肥大表型没有影响。因此，ROS在ARVM中介导对α（1）-AR刺激的肥大生长反应中起关键作用。(C)北京大学出版社.
Norepinephrine (NE) causes hypertrophic growth of cardiac myocytes via stimulation of alpha(1)-adrenergic receptors (alpha (1)-AR). Reactive oxygen species (ROS) can act as signaling molecules for cell growth. Accordingly, we tested the hypothesis that ROS mediate alpha (1)-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. alpha (1)-AR stimulation with NE (1 muM) in the presence of propranolol (2 muM) for 48-96 h caused a hypertrophic growth phenotype characterized by a 36 +/- 3% increase in H-3-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 alpha (1)-AR-selective antagonist prazosin (100 nM) or the SOD-mimetics MnTMPyP (50 muM) and Euk-8 (100 muM). MnTMPyP had no effect on alpha (1)-AR-stimulated H-3-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 alpha (1)-AR-stimulation in ARVM. (C) 2000 Academic Press.