H2O2-Induced ERK 1/2 MAP Kinases Activity Mediating the Interaction between Thioredoxin-1 and the Thioredoxin Interacting Protein

Thioredoxin-1 (Trx-1) and Txnip are critical to the redox regulation of cells. Regulation of the expression levels of Trx-1, Txnip, and of TrxRs by miRs is achieved under oxidative stress. H₂O₂, in a similar fashion as Nitric oxide (NO), affects nuclear migration of Trx-1. This is associated with intracellular compartmentalization and activation of extracellular signal–regulated kinases (ERK) 1/2 MAP kinases. The interaction of Trx-1 and Txnip coordinated by the ERK 1/2 MAP kinases is responsible for the nuclear migration of Trx-1 and cell survival. A general scheme illustrates how oxidative stress triggered by H₂O₂ or NO mediates Trx1/Txnip interactions associated with survival signalling. Thioredoxin interacting protein (Txnip) or thioredoxin binding protein 2 (TBP-2) is a vitamin D3 upregulated protein. Txnip is a negative regulator of Trx-1 and may be a suppressor of Trx-1-mediated prosurvival signalling. Peroxiredoxins are direct targets that function in the reduction of H₂O₂ and organic peroxides associated with redox signalling.