Myocardial protection during heart surgery by IGF-1 and bcl-2 gene introduction.
| Project/Area Number |
10671275
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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 | Kansai Medical University |
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Principal Investigator |
OTANI Hajime Kansai Medical University, School of medicine, assistant professor, 医学部, 講師 (60168979)
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| Co-Investigator(Kenkyū-buntansha) |
OSAKO Motohiko Kansai Medical University, School of medicine, research associate, 医学部, 助手 (90223784)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | myocardial ischemia / IGF-1 / Bcl-xL / Bax / Bcl-2 / IGF-I |
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| Research Abstract |
Insulin like growth factor-1 (IGF-1) has become a promising tool for treatment with end-stage heart failure. Although the underlying mechanism for myocardial protection remains elusive, recent studies suggest that altered regulation of Bcl-2 family proteins may be involved in the cytoprotective action of IGF-1. It has also been clear that intracellular localization of Bcl-2 family proteins is crucial in regulating the release of death-promoting cytochrome c from mitochondria. Therefore, we have investigated the effect of IGF-1 on Bcl-2 family protein expression and cytochrome c release in isolated rat heart mitochondria. Rats were treated with intra-peritoneal injection with IGF-1(3mg/kg). Mitochondria were isolated from the heart 12, 24, and 36 hours after the treatment. Western blot analysis showed that Bcl-xL expression was maximally increased in the rat heart mitochondria 24 hours after IGF-1 treatment, while Bax expression was maximally down-regulated in the same mitochondrial fra
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ction. Neither Bcl-xL nor Bax protein was detected in the cytosol fraction at any time point after IGF-1treatment. Bcl-2 protein was undetectable in mitochondria, cytosol, microsome or nuclearmyofibrillar fraction. Immunohistochemical staining revealed that IGF-1-induced overexpression of Bcl-xL in the heart was confined to cardiomyocytes. Isolated rat heart mitochondria did not release cytochrome c without a respiratory substrate succinate even in the presence of 10μM CaィイD12+ィエD1. However, respiring mitochondria released cytochrome c in a CaィイD12+ィエD1 dependent manner. Cytochrome c release was attenuated in mitochondria obtained from the heart treated with IGF-1. These results suggest that IGF-1 differentially regulates expression of Bcl-xL and Bax proteins in the rat heart mitochondria. IGF-1-Induced inhibition of cytochrome c release from the mitochondria may represent a mechanism for inhibition of apoptotic cardimyocyte cell death in patients with end-stage heart failure, or with reperfusion injury. Less
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Research Products
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