Document Detail


Thioredoxin 1 is essential for sodium sulfide-mediated cardioprotection in the setting of heart failure.
MedLine Citation:
PMID:  23349187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The aim of this study was to determine whether thioredoxin 1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H2S) in a model of ischemic-induced heart failure (HF).
APPROACH AND RESULTS: Mice with a cardiac-specific overexpression of a dominant negative mutant of Trx1 and wild-type littermates were subjected to ischemic-induced HF. Treatment with H2S as sodium sulfide (Na2S) not only increased the gene and protein expression of Trx1 in the absence of ischemia but also augmented the HF-induced increase in both. Wild-type mice treated with Na2S experienced less left-ventricular dilatation, improved left-ventricular function, and less cardiac hypertrophy after the induction of HF. In contrast, Na2S therapy failed to improve any of these parameters in the dominant negative mutant of Trx1 mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S therapy inhibited HF-induced apoptosis signaling kinase-1 signaling and nuclear export of histone deacetylase 4 in a Trx1-dependent manner.
CONCLUSIONS: These findings provide novel information that the upregulation of Trx1 by Na2S therapy in the setting of HF sets into motion events, such as the inhibition of apoptosis signaling kinase-1 signaling and histone deacetylase 4 nuclear export, which ultimately leads to the attenuationof left-ventricular remodeling.
Authors:
Chad K Nicholson; Jonathan P Lambert; Jeffery D Molkentin; Junichi Sadoshima; John W Calvert
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  33     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-14     Completed Date:  2013-05-02     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  744-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Animals
Cardiotonic Agents / metabolism,  pharmacology*
Disease Models, Animal
Genes, Reporter
Heart Failure / drug therapy*,  genetics,  metabolism,  physiopathology,  ultrasonography
Hemodynamics / drug effects
Histone Deacetylases / metabolism
Hydrogen Sulfide / metabolism
Hypertrophy, Left Ventricular / metabolism,  prevention & control
JNK Mitogen-Activated Protein Kinases / metabolism
Luciferases / genetics,  metabolism
MAP Kinase Kinase Kinase 5 / antagonists & inhibitors,  metabolism
Male
Mice
Mice, Transgenic
Mutation
Myocardium / metabolism*,  pathology
NFATC Transcription Factors / genetics
RNA, Messenger / metabolism
Signal Transduction / drug effects
Stroke Volume / drug effects
Sulfides / metabolism,  pharmacology*
Thioredoxins / genetics,  metabolism*
Time Factors
Up-Regulation
Ventricular Function, Left / drug effects
Ventricular Remodeling / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism
Grant Support
ID/Acronym/Agency:
5R01HL098481-03/HL/NHLBI NIH HHS; R01 HL098481/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/NFATC Transcription Factors; 0/RNA, Messenger; 0/Sulfides; 0/Txn1 protein, mouse; 52500-60-4/Thioredoxins; EC 1.13.12.-/Luciferases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.11.25/MAP Kinase Kinase Kinase 5; EC 2.7.11.25/Map3k5 protein, mouse; EC 3.5.1.98/Hdac5 protein, mouse; EC 3.5.1.98/Histone Deacetylases; YGR27ZW0Y7/sodium sulfide; YY9FVM7NSN/Hydrogen Sulfide
Comments/Corrections

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