| Identification of a NF-κB cardioprotective gene program: NF-κB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion. | |
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MedLine Citation:
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PMID: 21439970 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The transcription factor Nuclear Factor Kappa B (NF-κB) has been shown to be cardioprotective after permanent coronary occlusion (PO) and late ischemic preconditioning (IPC), and yet it is cell injurious after ischemia/reperfusion (I/R) in the heart. There is limited information regarding NF-κB-dependent cardioprotection, and the NF-κB-dependent genes that contribute to the cardioprotection after PO are completely unknown. The objective of the study was to identify NF-κB-dependent genes that contribute to cardioprotection after PO. Microarray analysis was used to delineate genes that potentially contribute to the NF-κB-dependent cardioprotection by determining the overlap between the set of PO regulated genes and genes regulated by NF-κB, using mice with genetic abrogation of NF-κB activation in the heart. This analysis identified 16 genes as candidates for NF-κB-dependent effects after PO. This set of genes overlaps with, but is significantly different from the set of genes we previously identified as regulated by NF-κB after IPC. The genes encoding heat shock protein 70.3 (hspa1a) and heat shock protein 70.1 (hspa1b) were the most significantly regulated genes after PO and were up-regulated by NF-κB. Results using knockout mice show that Hsp70.1 contributes to NF-κB-dependent cardioprotection after PO and likely underlies, at least in part, the NF-κΒ-dependent cardioprotective effect. Our previous results show that Hsp70.1 is injurious after I/R injury. This demonstrates that, like NF-κB itself, Hsp70.1 has antithetical effects on myocardial survival and suggests that this may underlie the similar antithetical effects of NF-κB after different ischemic stimuli. The significance of the research is that understanding the gene network regulated by NF-κB after ischemic insult may lead to identification of therapeutic targets more appropriate for clinical development. |
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Authors:
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Michael E Wilhide; Michael Tranter; Xiaoping Ren; Jing Chen; Maureen A Sartor; Mario Medvedovic; W Keith Jones |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-03-23 |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 51 ISSN: 1095-8584 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-05-27 Completed Date: 2011-09-14 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
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Languages: eng Pagination: 82-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Pharmacology & Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiotonic Agents / metabolism Coronary Occlusion / metabolism* Gene Regulatory Networks HSP70 Heat-Shock Proteins / genetics, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Microarray Analysis Myocardial Reperfusion Injury / genetics, metabolism* NF-kappa B / genetics, metabolism* Polymerase Chain Reaction Transcriptional Activation |
| Grant Support | |
ID/Acronym/Agency:
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HL081923/HL/NHLBI NIH HHS; HL091478/HL/NHLBI NIH HHS; HL63034/HL/NHLBI NIH HHS; R01 HL063034-09/HL/NHLBI NIH HHS; R01 HL091478-01A1/HL/NHLBI NIH HHS; R01 HL091478-01A1S1/HL/NHLBI NIH HHS; R01 HL091478-02/HL/NHLBI NIH HHS; R01 HL091478-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/HSP70 Heat-Shock Proteins; 0/NF-kappa B; 0/heat-shock protein 70.1 |
| Comments/Corrections | |
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