Interacting with thioredoxin-1--disease or no disease?

Antioxid Redox Signal. 2013 Mar 20;18(9):1053-62. doi: 10.1089/ars.2012.4822. Epub 2012 Sep 24.

Abstract

Significance: Many cardiovascular disorders are accompanied by a deregulated cellular redox balance resulting in elevated levels of intracellular reactive oxygen species (ROS). One major antioxidative cellular molecule is thioredoxin-1 (Trx-1). Its indispensability is demonstrated by the embryonic lethality of Trx-1 deficient mice. Trx-1 is ubiquitously expressed in cells and has numerous, diverse functions. It not only reduces oxidized proteins or, together with peroxiredoxins, detoxifies H(2)O(2), but also binds to several proteins and thereby regulates their functions. The interaction partners of Trx-1 differ depending on its localization in the cytosol or in the nucleus.

Recent advances/critical issues: Over the past decade it has become clear that Trx-1 is not only critical for tumor functions, which has resulted in therapeutic approaches targeting this protein, but also essential for proper functions of the vasculature and the heart. Changes in post-translational modifications of Trx-1 or in its interactions with other proteins can lead to a switch from a physiologic state of cells and organs to diverse pathologies. This review provides insights into the role of Trx-1 in different physiological situations and cardiac hypertrophy, ischemia reperfusion injury, heart failure, atherosclerosis, and diabetes mellitus type 2, underscoring the central role of Trx-1 in cardiovascular health and disease.

Future directions: Thus, the manipulation of Trx-1 activity in the heart and/or vasculature, for example, by small molecules, seems to be a promising therapeutic option in cardiovascular diseases, as general anti-oxidant treatments would not take into account interactions of Trx-1 with other proteins and also eliminate vital ROS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / metabolism
  • Blood Vessels / metabolism
  • Cardiovascular System / metabolism*
  • Cysteine / metabolism
  • Cystine / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Heart Diseases / drug therapy
  • Heart Diseases / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Mice
  • Models, Cardiovascular
  • Molecular Targeted Therapy
  • Myocardium / metabolism
  • NADP / metabolism
  • Neoplasm Proteins / physiology
  • Neoplasms / metabolism
  • Oxidation-Reduction
  • Peroxiredoxins / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Thioredoxins / physiology*

Substances

  • Neoplasm Proteins
  • Reactive Oxygen Species
  • Cystine
  • Thioredoxins
  • NADP
  • Hydrogen Peroxide
  • Peroxiredoxins
  • Cysteine