Mechanism in transition of hypertrophied myocardium to failing heart and oxidative stress
| Project/Area Number |
12671290
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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 |
Thoracic surgery
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| Research Institution | Hirosaki University |
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Principal Investigator |
TSHUSHIMA Takao (2001-2002) Hirosaki University School of Medicine Hospital, 1^<st> department of Surgery, Assistant Professor, 医学部附属病院, 講師 (70236876)
竹内 功 (2000) 弘前大学, 医学部, 助手 (10302027)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | hypertrophied myocardium / failing heart / oxidative stress / apoptosis / ERKs / glucose metabolism / 肥大心筋 / Oxidative / Oxidative Stress |
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| Research Abstract |
Signaling pathway for adaptive response to pressure or volume overload towards a hypertrophied myocardium have been actively studied for many years. However, the mechanisms of transition from compensated to decompensated hypertrophied heart remain unclear. In hypertrophied myocardium the glycolytic use of exogenous glucose is known to be increased more than the oxidative use of exogenous fatty acid and becomes a more preferable substrate to maintain the high phosphates. On the other hand, in failing heart glucose metabolism has tendency to deteriorate. Oxidative stress is one of the mechanism for developing hypertrophied heart and several oxyradicals are known to stimulate glucose uptake and apoptosis in other cell types. We hypothesized that hydrogen peroxide (H_2O_2) improving glucose uptake can be oxidative stress to cause apoptotic cell death in a transition from compensated to decompensated hypertrophied myocardium. We used two different models such as pressure overload hypertroph
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ied rat heart model (by aortic banding) and isoproterenol stimulated cultured myoblasts (H9c2) model to focus on glucose metabolism, apoptosis, extracellular signal-regulated protein kinases (ERKs) and myocardial function in relation of H_2O_2.
H_2O_2 production was increased in a transition from compensated to decompensated hypertrophied heart and associated with temporary suppression of ERKs in pressure overload hypertrophied heart mode. In cultured myoblasts, anaerobic glycolysis became prominent at day 7 isoproterenol stimulation (ISO7). H_2O_2 production started to be increased at day 5 isoproterenol stimulation (ISO5) and peaked at ISO7. Apoptotic cell death was significantly increased in ISO5 and ISO7. Temporary ERKs suppression was also found at ISO5 and ISO7. Change in glucose metabolism leads to stimulation of H_2O_2 production, apoptotic cell death and suppression of ERKs.
We conclude that hydrogen peroxide production was increased in transition of hypertrophied myocytes to decompensated hypertrophied myocardium in association with impaired glucose metabolism, increased apoptotic cell death. Suppression of ERKs may be involved in signal transduction of apoptotic cell death. Less
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Report
(4 results)
Research Products
(4 results)
