Thioredoxin 1 is essential for sodium sulfide-mediated cardioprotection in the setting of heart failure

Chad K. Nicholson, Jonathan P. Lambert, Jeffery D. Molkentin, Junichi Sadoshima, John W. Calvert

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)744-751
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2013

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Keywords

  • apoptosis signaling kinase-1
  • heart failure
  • histone deacetylase 4
  • hydrogen sulfide
  • left ventricular remodeling
  • nuclear factor of activated T cells
  • thioredoxin 1

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