Regulation of the human thioredoxin gene promoter and its key substrates: A study of functional and putative regulatory elements (original) (raw)

“…The increased expression of Trx1 observed here corresponds to the downregulation of the TXNIP gene, which codes for an endogenous inhibitor of Trx1 found in cells treated with TEGDMA [38]. Upregulation of TrxR1 completed a system to regenerate reduced Trx1, and the expression of both proteins with no detectable influence of BSO, OTC or NAC indicated a very sensitive induction of the expression though Nrf2 [22]. Glutathione reductase (GR) expression is evidently constitutively kept at high levels under normal and wide-ranging oxidative stress conditions initiated by HEMA to maintain high concentrations of GSH and low levels of the oxidized glutathione disulfide (GSSG) [44].…”

Section: Expression Of Nrf2 In Hema-exposed Mouse Macrophagesmentioning

“…The expression of H 2 O 2 -removing enzymes is supported by the expression of enzymes from the thioredoxin system counteracting oxidative stress through the activation of thioredoxin 1 (Trx1) and thioredoxin reductase (TrxR1) [22]. It is plausible that Trx1 expression is upregulated in HEMA-exposed cells to regenerate Cys-SH groups in Prxd1 after oxidation through the removal of H 2 O 2 .…”

Section: Expression Of Nrf2 In Hema-exposed Mouse Macrophagesmentioning

“…The Nrf2 is a transcription factor known to be a key regulator of antioxidative genes, including HO-1, NQO1, TXN, and GCLC. [24][25][26] In a nonstimulated state, Nrf2 protein is sequestered in the cytoplasm through binding to Keap1 protein. 25 Once the Nrf2 pathway is activated, Nrf2 disassociates from Keap1 and moves into the nucleus where it can regulate gene transcription.…”

Section: Discussionmentioning

“…NRF2 also promotes the expression of glutathione peroxidase, glutathione reductase, and thioredoxin reductase ( Fig. 1; Hayes and McMahon 2009;Abbas et al 2011;Jeong et al 2012;Hawkes et al 2014;Lu and Holmgren 2014), as well as proteins such as ferritin, which blocks the formation of free radicals, and NADPH:quinone oxidoreductase 1, which inhibits the Figure 1. Endogenous antioxidant mechanisms.…”

Section: Antioxidant Mechanisms For Ros Defensementioning