2000 Fiscal Year Final Research Report Summary
Novel mechanism on the ischemic preconditioning : Role of AMP deaminase family for adenosine production
| Project/Area Number |
11670680
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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 | Tottori University |
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Principal Investigator |
HISATOME Ichiro Tottori University, The 1^<st> Department of Medicine, Associate Professor, 医学部, 助教授 (60211504)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yasonori Tottori University, The 1<@D1st@>D1 Department of Medicine, Research Associate, 医学部, 助手 (60294310)
OHTAHARA Akira Tottori University, The 1<@D1st@>D1 Department of Medicine, Research Associate, 医学部・附属病院, 助手
OGINO Kazuhide Tottori University, The 1<@D1st@>D1 Department of Medicine, Assistant Professor, 医学部, 講師 (70294311)
TANIGUCHI Shin-ichi Tottori University, The 1<@D1st@>D1 Department of Medicine, Research Associate, 医学部, 助手 (30304207)
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| Project Period (FY) |
1999 – 2000
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| Keywords | AMP deaminase / Ischemic preconditioning / myosin heary chain / human heat |
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| Research Abstract |
Adenosine is known to be the mediator to facilitate the ischemic preconditioning of the heart. Adenosine is converted from extracellular AMP by ecto 5'-nucleotidase, and is also produced from intracellular adenosine monophosphate (AMP) by cytosolic 5'-nucleotidase, suggesting adenosine concentration will be influenced by intracellular AMP concentration. AMP concentration can be degradated not only by cytosolic 5'-nucleotidase into adenosine but also by AMP deaminase into inosine monophosphate (IMP). Therefore, adenosine concentration would be decreased by the activation of AMP deaminase. AMP deaminase family is composed of muscular AMPD1, hepatic AMPD2 and blood type AMPD3. However the distribution and function of cardiac AMP deaminase is not still characterized. In the present study, we studied the localization and the function of cardiac AMP deaminase. While the right atrium expressed the message and the protein of AMPD1, 2, and 3, the left atrium and both ventricles expressed AMPD2
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and 3 in patients with heart failure. AMPD1 has the myosin heavy chain binding site which included the consensus sequence of PVEK.Based on the alignment for the amino acid sequence, AMPD2 and 3 possess the myosin binding site as well. The heterologous expression study of both AMP deaminase family and myosin heavy chain showed that AMPD3 can bind the myosin heavy chain as AMPD1, but AMPD2 did not bind to myosin heavy chain. While the activity of myosin heavy chain-bound AMPD1 was significantly higher than that of unbound AMPD1, the activity of AMPD3 did not alter under either myosin heavy chain bound or unbound condition. Under ischemic condition of the heart myosin bound AMP deaminase activity (AMPD3 dominantly expressed) did not change, although under ischemic condition of the skeletal muscle myosin bound AMP deaminase activity (dominantly AMPD1 expressed) significantly elevated. In addition AMPD 3 can bind to ecto 5'- nucleotidase, as AMPD1 and 2 can bind to it. These results suggest that cardiac ischemia facilitated myosin heavy chain to bind to AMPD3 in order to both ecto and cytosolic 5'-nucleotidase can utilize the AMP to convert into adenosine, which would lead to activate the ischemic preconditioning of the heart. Less
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