| Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1. | |
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MedLine Citation:
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PMID: 18931029 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ischemic tolerance decreases with aging, and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in middle-aged animals. We have demonstrated that short-term caloric restriction (CR) improves myocardial ischemic tolerance in young and old animals via the activation of adiponectin-AMP-activated protein kinase (AMPK)-mediated signaling. However, it is unknown whether prolonged CR confers cardioprotection in a similar manner. Furthermore, little is known regarding the myocardial expression of silent information regulator 1 (Sirt1; which reportedly mediates various aspects of the CR response) with prolonged CR. Thus, 6-mo-old male Fischer-344 rats were randomly divided into ad libitum (AL) and CR groups. Six months later, isolated perfused hearts were subjected to 25 min of global ischemia followed by 120 min of reperfusion with or without IPC. CR improved the recovery of left ventricular function and reduced infarct size after ischemia-reperfusion and restored the IPC effect. Serum adiponectin levels increased, but myocardial levels of total and phosphorylated AMPK did not change with prolonged CR. Total levels of Sirt1 did not change with CR; however, in the nuclear fraction, CR significantly increased Sirt1 and decreased acetyl-histone H3. Eleven rats from each group were given N-nitro-l-arginine methyl ester in their drinking water for 4 wk before death. In these hearts, chronic inhibition of nitric oxide synthase prevented the increase in nuclear Sirt1 content by CR and abrogated CR-induced cardioprotection. These results demonstrate that 1) prolonged CR improves myocardial ischemic tolerance and restores the IPC effect in middle-aged rats and 2) CR-induced cardioprotection is associated with a nitric oxide-dependent increase in nuclear Sirt1 content. |
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Authors:
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Ken Shinmura; Kayoko Tamaki; Roberto Bolli |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-17 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 295 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-05 Completed Date: 2009-01-30 Revised Date: 2012-04-09 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2348-55 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. shimmura@sc.itc.keio.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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metabolism Acetyl-CoA Carboxylase / metabolism Adiponectin / blood Animals Caloric Restriction* Caspase 3 / metabolism Cell Nucleus / enzymology Cytochromes c / metabolism Disease Models, Animal Enzyme Inhibitors / pharmacology Ischemic Preconditioning, Myocardial* Male Myocardial Ischemia / enzymology, pathology, physiopathology, prevention & control* Myocardial Reperfusion Injury / enzymology, pathology, physiopathology, prevention & control* Myocardium / enzymology*, pathology NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / metabolism* Nitric Oxide Synthase / antagonists & inhibitors, metabolism Phosphorylation Rats Rats, Inbred F344 Sirtuin 1 Sirtuins / metabolism* Time Factors Up-Regulation Ventricular Function, Left |
| Grant Support | |
ID/Acronym/Agency:
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HL-55757/HL/NHLBI NIH HHS; HL-70897/HL/NHLBI NIH HHS; HL-76794/HL/NHLBI NIH HHS; HL-78825/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Adipoq protein, rat; 0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 9007-43-6/Cytochromes c; EC 1.14.13.39/Nitric Oxide Synthase; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.5.1.-/Sirt1 protein, rat; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuins; EC 6.4.1.2/Acetyl-CoA Carboxylase |
| Comments/Corrections | |
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