Key result
Antioxidant treatment prevents cardiac hypertrophy in rat myocytes by suppressing ROS and blocking ERK activation.
Why the study?
ROS modulate hypertrophic signaling in neonatal cardiac myocytes, but findings may not reflect mature myocardium due to inherent differences between neonatal and adult cells.
Does ROS mediate signal transduction of cardiac hypertrophy induced by ET-1 or PE in adult rat cardiac myocytes?
Does ROS mediate signal transduction of cardiac hypertrophy induced by ET-1 or PE in adult rat cardiac myocytes?
Reactive oxygen species derived from NADH/NADPH oxidase mediate hypertrophic signaling via ERK activation in adult rat cardiac myocytes.
OBJECTIVES: We analyzed the regulatory function of reactive oxygen species (ROS) on the hypertrophic signaling in adult rat cardiac myocytes: BACKGROUND: The ROS regulate mitogenic signal transduction in various cell types. In neonatal rat cardiac myocyte, antioxidants have been shown to inhibit cardiac hypertrophy, and ROS are suggested to modulate the hypertrophic signaling. However, the conclusion may not reflect the situation of mature heart, because of the different natures between neonatal and adult cardiac myocytes. METHODS: Cultured adult rat cardiac myocytes were stimulated with endothelin-1 (ET-1) or phenylephrine (PE), and intracellular ROS levels, the activities of mitogen-activated protein kinases (MAPKs; ERK, p38, and JNK), and 3H-phenylalanine incorporation were examined. We also examined the effects of antioxidant pretreatment of myocytes on MAPK activities and cardiac hypertrophy to analyze the modulatory function of redox state on MAPK-mediated hypertrophic signaling. RESULTS: The ROS levels in ET-1- or PE-stimulated myocytes were maximally increased at 5 min after stimulation. The origin of ROS appears to be from NADH/NADPH oxidase, because the increase in ROS was suppressed by pretreatment of myocytes with NADH/NADPH oxidase inhibitor diphenyleneiodonium. Extracellular signal-regulated kinase (ERK) activity was increased by the stimulation of ET-1 or PE. In contrast, p38 and c-Jun-N-terminal protein kinase (JNK) activities did not change after these stimulations. Antioxidant treatment of myocytes suppressed the increase in ROS and blocked ERK activation and the subsequent cardiac hypertrophy induced by these stimuli. CONCLUSIONS: These data demonstrate that ROS mediate signal transduction of cardiac hypertrophy induced by ET-1 or PE in adult rat cardiac myocytes.
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Tanaka et al. (2001) studied Cardiac hypertrophy. Endothelin-1 (ET-1) or phenylephrine (PE) with or without antioxidant pretreatment vs. Unstimulated or non-pretreated myocytes was evaluated on Intracellular ROS levels, MAPK activities, and 3H-phenylalanine incorporation. In cultured adult rat cardiac myocytes, antioxidant treatment suppressed the ET-1- or PE-induced increase in ROS, blocked ERK activation, and prevented subsequent cardiac hypertrophy.
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