About this item:

412 Views | 366 Downloads

Author Notes:

Email Address: David J. Lefer : dlefe1@lsuhsc@.edu

Subjects:

Research Funding:

This work was supported by grants from the National Heart, Lung, and Blood Institute (National Institutes of Health; 1R01 HL092141 (Lefer), 1R01 HL093579 (Lefer), 1U24 HL 094373 (Lefer), 1P20 HL113452 (Lefer), and 1KO8HL119592 (Brewster)

Supported in part by PHS (Public Health Service) Grant UL1TR000454 from the Clinical and Translational Science Award Program, National Institutes of Health, National Center for Advancing Translational Sciences (Brewster) and the American Heart Association 13IRG14740001 (Brewster).

Keywords:

  • antioxidant proteins
  • critical limb ischemia
  • hydrogen sulfide
  • NRF2
  • oxidative stress

Hydrogen Sulfide Levels and Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI)

Tools:

Journal Title:

Journal of the American Heart Association

Volume:

Volume 4, Number 5

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

BACKGROUND: Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen sulfide (H2S). Functions of H2S are mediated by several targets including ion channels and signaling proteins. Nuclear factor-erythroid 2-related factor 2 is responsible for the expression of antioxidant response element-regulated genes and is known to be upregulated by H2S. We examined the levels of H2S, H2S-producing enzymes, and nuclear factor-erythroid 2-related factor 2 activation status in skeletal muscle obtained from critical limb ischemia (CLI) patients. METHODS AND RESULTS: Gastrocnemius tissues were attained postamputation from human CLI and healthy control patients. We found mRNA and protein levels of cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase were significantly decreased in skeletal muscle of CLI patients as compared to control. H2S and sulfane sulfur levels were significantly decreased in skeletal muscle of CLI patients. We also observed significant reductions in nuclear factor-erythroid 2-related factor 2 activation as well as antioxidant proteins, such as Cu, Zn-superoxide dismutase, catalase, and glutathione peroxidase in skeletal muscle of CLI patients. Biomarkers of oxidative stress, such as malondialdehyde and protein carbonyl formation, were significantly increased in skeletal muscle of CLI patients as compared to healthy controls. CONCLUSIONS: The data demonstrate that H2S bioavailability and nuclear factor-erythroid 2-related factor 2 activation are both attenuated in CLI tissues concomitant with significantly increased oxidative stress. Reductions in the activity of H2S-producing enzymes may contribute to the pathogenesis of CLI.

Copyright information:

© 2015 The Authors.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits distribution of derivative works, making multiple copies, distribution, public display, and publicly performance, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author. This license prohibits exercising rights for commercial purposes.

Creative Commons License

Export to EndNote