The Change of Hypertrophic Signaling during the Development of Cardiac Hypertrophy and Its Regulation by Reactive Oxygen Species
| Project/Area Number |
12670670
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Shimane Medical University |
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Principal Investigator |
TANAKA Koichi Shimane Medical University, School of Medicine, Instructor, 医学部, 助手 (00252924)
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| Co-Investigator(Kenkyū-buntansha) |
HONDA Masaaki Shimane Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (90127530)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | cardic hypertrophy / reactive oxygen species / MAPK / MAPK |
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| Research Abstract |
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 myocytes, 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 nature 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 stimulation. Antioxidant treatment of myocytes suppressed the increase in ROS and blocked ERK activation and 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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Report
(3 results)
Research Products
(4 results)
