Clarification of cascade for myocardial infarction related molecules, lymphotoxin-a and galectin-2.
| Project/Area Number |
17390238
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | RIKEN |
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Principal Investigator |
OZAKI Kouichi RIKEN, Laboratory for Cardiovascular Diseases, 心筋梗塞関連遺伝子研究チーム, 上級研究員 (50373288)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2005: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | lymphotoxin-alpha / galectin-2 / myocardial infarction / inflammation / toll like receptor / MAP3K7 / NFkB / リンフォトキシン-α(LTA) / Tandem affinity purification法 |
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| Research Abstract |
Myocardial infarction might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by each of themselves. We have previously identified galectin-2 protein as a binding partner of lymphotoxin-alpha (LTA) whose functional single nucleotide polymorphisms (SNPs) conferred susceptibility to myocardial infarction. The association study further revealed that a functional SNP in LGALS2 encoding galectin-2, which led to altered secretion of LTA, was also indicated a risk of myocardial infarction. To clarify detailed function of galectin-2 protein, we searched for its binding partners by using a tandem affinity purification method and identified toll like receptor 1, 2 (TLR1, 2), leprtin receptor (LEPR) and mitogen activated kinase kinase kinase 7 (MAP3K7), which plays an important role in inflammation and immune systems. I also found that knock-down of MAP3K7 protein level using siMAP3K7 inhibited the activation of NFkB, an important transcription factor in inflammation, in human coronary artery endotherial cells. Combined with previous results that LTA and tubulins also bind with galectin-2 and that tubulins have been reported to be used in the intracellular transport of membrane protein, we hypothesized galectin-2 plays a pivotal role in the transport of various proteins that constitute immune system including inflammation.
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Report
(3 results)
Research Products
(14 results)
