| Involvement of GSK-3β in attenuation of the cardioprotective effect of ischemic preconditioning in diabetic rat heart. | |
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MedLine Citation:
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PMID: 20512612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthase kinase-3β (GSK-3β) that inhibits the opening of mitochondrial permeability transition pore (MPTP). The activity of glycogen GSK-3β is elevated during diabetes mellitus (DM). This study investigated the role of GSK-3β in attenuation of cardioprotective effect of IPC in diabetic rat. DM was induced by single administration of streptozotocin (STZ, 50 mg/kg, i.p.). Isolated perfused heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed in coronary effluent. IPC significantly decreased myocardial infarct size and release of LDH and CK-MB from normal rat heart. The cardioprotective effect of IPC was significantly attenuated in diabetic rat. Four episodes of preconditioning by either of GSK-3β inhibitors, lithium chloride (LiCl, 20 mM), indirubin-3 monooxime (1 μM), and SB216763 (3 μM) significantly reduced the LDH and CK-MB release and decreased infarct size in diabetic rat heart. Perfusion of atractyloside, an opener of MPTP, significantly attenuated, the cardioprotective effect of IPC in normal rat heart, and of GSK-3β inhibitor induced preconditioning in the DM rat heart. Our results suggest that preconditioning with GSK-3β inhibitors in diabetic rat heart may provide a more consistent cardioprotection, as compared to IPC. Also, the mechanism of diabetes mellitus-induced attenuation of cardioprotective effect of IPC involves activation of GSK-3β, due to impaired protective upstream signaling pathways and opening of MPTP during reperfusion. |
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Authors:
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Harlokesh Narayan Yadav; Manjeet Singh; P L Sharma |
Publication Detail:
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Type: Journal Article Date: 2010-05-30 |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: 343 ISSN: 1573-4919 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-21 Completed Date: 2011-03-01 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 75-81 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, ISF College of Pharmacy, Ghal Kalan, Moga, Punjab, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atractyloside / pharmacology Blood Glucose / metabolism Creatine Kinase, MB Form / metabolism Diabetes Mellitus, Experimental / enzymology* Enzyme Inhibitors / pharmacology Glycogen Synthase Kinase 3 / metabolism* Ischemic Preconditioning* L-Lactate Dehydrogenase / metabolism Phosphorylation Rats Streptozocin |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Enzyme Inhibitors; 17754-44-8/Atractyloside; 18883-66-4/Streptozocin; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 2.7.3.2/Creatine Kinase, MB Form |
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