title: Interacting with thioredoxin-1--disease or no disease?
abstract: CONCLUSIONS
  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.
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Cell and Aging Research, IUF--Leibniz Research Institute for Environmental Medicine, University of Duesseldorf gGmbH, Duesseldorf, Germany.
authors.forename: Tim-Christian
authors.initials: TC
authors.lastname: Zschauer
authors.forename: Shouji
authors.initials: S
authors.lastname: Matsushima
authors.forename: Joachim
authors.initials: J
authors.lastname: Altschmied
authors.forename: Dan
authors.initials: D
authors.lastname: Shao
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D003553:Cystine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008955:Models, Cardiovascular; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D003553:Cystine; D013879:Thioredoxins; D009249:NADP; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D003545:Cysteine