1998 Fiscal Year Final Research Report Summary
Mechanism of ischemic preconditioning mediated by protein kinase C activation caused by ischemia-related lipid metabolites.
| Project/Area Number |
08457014
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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 |
General physiology
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| Research Institution | Oita Medical University |
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Principal Investigator |
ARITA Makoto Oita Medical University, Professor, 医学部, 教授 (60037364)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Toshio Oita Medical University, Assistant, 医学部, 助手 (80169359)
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| Project Period (FY) |
1996 – 1998
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| Keywords | microdialysis / lysophosphatidylcholine / protein kinase C / ecto-5'-nucleotidase / adenosine / chelerythrine / rat heart / ischemic preconditioning |
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| Research Abstract |
1. Adenosine plays a crucial role in the evolution of ischemic preconditioning. With the use of microdialysis teci-miques in in situ rat hearts, we assessed the activity of ecto-5'-nucleotidase (a key enzyme responsible for adenosine production), and examined the effects of lysophosphatidyicholine (LPC) on the production of interstitial adenosine.
2. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and perfused with Tyrode solution containing adenosine 5'-monophosphate (AMP, 100 muM). With this system, the dialysate adenosine was considered to originate from the dephosphorylation of AMP, catalyzed by endogenous ecto-5'-nucleotidase, and the level of dialysate adenosine was verified to be a handy measure of the ecto-5'-nucleotidase activity in VIVO.
3. LPC at concentrations of 25 and 50 muM significantly increased the level of dialysate adenosine to 122.7 * 4.3 % (n=4, p<O.05) and 158.6 * 7.2 % (n=5, p<O.O5) of the control value, respectively. Chelerythrine (200 muM), a protein kinase C (PKC) inhibitor, completely abolished the increase of dialysate adenosine afforded by LPC (50 muM) (n=5).
4. These data provide the first evidence that LPC does increase the concentration of interstitial adenosine via the PKC-mediated activation of endogenous ecto-5'-nucleotidase, in in situ rat hearts.
5. Thus, it is suggested that LPC accumulated in ischemic region plays a role for evolution of ischemic preconditioning via increased interstitial concentration of adenosine, a key compound responsible for ischemic preconditioning.
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