Downregulation of cardiac lineage protein-1 confers cardioprotection through the upregulation of redox effectors.
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.
Gurusamy
Narasimman
N
Cardiovascular Research Center, University of Connecticut, School of Medicine, Farmington, CT 06030-1110, USA.
Lekli
Istvan
I
Ahsan
Md Kaimul
MK
Ray
Diptarka
D
Mukherjee
Subhendu
S
Mascareno
Eduardo
E
Siddiqui
M A Q
MA
Das
Dipak K
DK
D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology; D019610:Cytoprotection; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D015536:Down-Regulation; D015195:Drug Design; D054477:Glutaredoxins / Q000378:metabolism; D006579:Heterozygote; D051379:Mice; D008817:Mice, Mutant Strains; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D050983:NF-E2 Transcription Factor / Q000378:metabolism; D016601:RNA-Binding Proteins; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D002316:Cardiotonic Agents; D054477:Glutaredoxins; C118642:Hexim1 protein, mouse; D050983:NF-E2 Transcription Factor; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D013879:Thioredoxins; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase