trans-Resveratrol downregulates Txnip overexpression occurring during liver ischemia-reperfusion.
Txnip (thioredoxin-interacting protein) is a protein with multifunctional roles in cellular responses and stress-related diseases. Txnip is involved in intracellular redox regulation and has been recently described as a possible link between redox state and metabolism. trans-Resveratrol (T-res) is a natural phytoalexin with antiproliferative, antiapoptotic and antioxidative effects. However, to date there have been no reports of the implication of Txnip in a model of liver acute stress such as ischemia-reperfusion (I/R) and no work has looked for a T-res effect on Txnip. Here we studied the effects of a post-ischemic treatment of T-res on the liver thioredoxin (Trx)/Txnip system and investigated whether the T-res effects were dependent on *NO production. In this work, liver I/R induced hepatic Txnip expression and T-res inhibited I/R Txnip expression. This decrease in Txnip expression by T-res was associated with an increase in liver Trx redox activity and a decrease in hepatic I/R-induced Trx-1 expression with no effect on Trx-2, on plasma Trx redox activity or on liver and plasma Trx reductase activity, independently of *NO production. In conclusion, these results show that in our model, not only did T-res protect Trx redox activity by diminishing the Txnip protein expression; it also reduced secretion of Trx1. This is the first report of a major implication of the Trx1/Txnip system in hepatic I/R injuries. It also affirms the importance of the antioxidant effect of T-res on the Trx1/Txnip system.
Nivet-Antoine
Valérie
V
Equipe d'accueil 4466 Faculté de Pharmacie, Université Paris Descartes, Paris, France. valerie.nivet-antoine@parisdescartes.fr
Cottart
Charles-Henry
CH
Lemaréchal
Hervé
H
Vamy
Michel
M
Margaill
Isabelle
I
Beaudeux
Jean-Louis
JL
Bonnefont-Rousselot
Dominique
D
Borderie
Didier
D
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D018797:Cell Cycle Proteins; D015536:Down-Regulation; D007275:Injections, Intravenous; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000097:blood / Q000378:metabolism; D013879:Thioredoxins / Q000097:blood / Q000378:metabolism
D000975:Antioxidants; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D013267:Stilbenes; C493796:TXNIP protein, rat; D009569:Nitric Oxide; D013879:Thioredoxins; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D013880:Thioredoxin-Disulfide Reductase; D000581:Amidohydrolases; C059999:dimethylargininase; D000077185:Resveratrol