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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 8475125, 11 pages
Review Article

Cell Signaling with Extracellular Thioredoxin and Thioredoxin-Like Proteins: Insight into Their Mechanisms of Action

1INSERM, U968, Sorbonne Universités, 75012 Paris, France
2UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France
3CNRS, UMR_7210, 75012 Paris, France

Correspondence should be addressed to Thierry Léveillard; rf.mresni@drallievel.yrreiht

Received 24 May 2017; Revised 6 July 2017; Accepted 17 July 2017; Published 12 September 2017

Academic Editor: Sergio Di Meo

Copyright © 2017 Thierry Léveillard and Najate Aït-Ali. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Thioredoxins are small thiol-oxidoreductase enzymes that control cellular redox homeostasis. Paradoxically, human thioredoxin (TXN1) was first identified as the adult T cell leukemia-derived factor (ADF), a secreted protein. ADF has been implicated in a wide variety of cell-to-cell communication systems acting as a cytokine or a chemokine. TRX80 is a truncated TXN1 protein with cytokine activity. The unconventional secretion mechanism of these extracellular thioredoxins is unknown. The thioredoxin system is relying on glucose metabolism through the pentose phosphate pathway that provides reducing power in the form of NADPH, the cofactor of thioredoxin reductase (TXNRD). While a complete extracellular TXN system is present in the blood in the form of circulating TXN1 and TXNDR1, the source of extracellular NADPH remains a mystery. In the absence of redox regenerating capacity, extracellular thioredoxins may rather be prooxidant agents. Rod-derived cone viability factor (RdCVF) is the product of intron retention of the nucleoredoxin-like 1 (NXNL1) gene, a secreted truncated thioredoxin-like protein. The other product encoded by the gene, RdCVFL, is an enzymatically active thioredoxin. This is a very singular example of positive feedback of a superthioredoxin system encoded by a single gene likely emerging during evolution from metabolic constraints on redox signaling.