Abstract
CLP-1, the mouse homologue of human Hexim1 protein, exerts inhibitory control on transcriptional elongation factor-b of RNA transcript elongation. Previously, we have demonstrated that downregulation of cardiac lineage protein-1 (CLP-1) in CLP-1(+/-) heterozygous mice affords cardioprotection against ischemia-reperfusion injury. Our current study results show that the improvement in cardiac function in CLP-1(+/-) mice after ischemia-reperfusion injury is achieved through the potentiation of redox signaling and their molecular targets including redox effector factor-1, nuclear factor erythroid 2-related factor, and NADPH oxidase 4 and the active usage of thioredoxin-1, thioredoxin-2, glutaredoxin-1 and glutaredoxin-2. Our results suggest that drugs designed to down regulate CLP-1 could confer cardioprotection through the potentiation of redox cycling.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cardiotonic Agents / chemistry
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Cardiotonic Agents / pharmacology
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Cytoprotection*
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DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
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Down-Regulation
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Drug Design
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Glutaredoxins / metabolism
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Heterozygote
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Mice
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Mice, Mutant Strains
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NADPH Oxidase 4
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NADPH Oxidases / metabolism
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NF-E2 Transcription Factor / metabolism
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RNA-Binding Proteins
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Reperfusion Injury / genetics
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Reperfusion Injury / metabolism*
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Thioredoxins / metabolism
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Up-Regulation
Substances
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Cardiotonic Agents
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Glutaredoxins
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Hexim1 protein, mouse
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NF-E2 Transcription Factor
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RNA-Binding Proteins
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Transcription Factors
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Thioredoxins
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NADPH Oxidase 4
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NADPH Oxidases
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Nox4 protein, mouse
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Apex1 protein, mouse
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DNA-(Apurinic or Apyrimidinic Site) Lyase