
-   The mRNA expression levels of Gpx2 was increased in GST-P-positive tumors or GST-P-positive lesions in rats after administration of peroxisome proliferator fenofibrate. The increase was acompanied by nuclear localization of transcription factor Nrf2 [PMID: 18775883].
-   GPx2 transcriptional regulation pathways are linked to thiol oxidation by oxidizing compounds released by inflammatory cells, or reactive oxygen species produced by cancer cells. In the Nrf2 pathway, Keap1 sequesters Nrf2 in the cytosol and prepares it for degradation. Upon oxidation of specific thiols in Keap1, Nrf2 is released and translocated into the nucleus to activate target genes [PMID: 19001094]. Similarly, reduced nucleoredoxin (Nrx) blocks disheveled (Dvl), which otherwise would transduce Wnt signals [PMID: 16604061]. Upon oxidation of Nrx by NADPH oxidase (Nox) 1-derived H2O2, Dvl is released and inhibits glycogen synthase kinase (GSK)-3beta in the beta-catenin degradation complex. Thereby, beta-catenin is stabilized and can activate target genes [PMID: 22278940].
-   GPx2 loss stimulates malignant progression in breast cancer due to reactive oxygen species/hypoxia inducible factor-alpha (HIF1alpha)/VEGFA signaling, causing poor perfusion and hypoxia, which were reversed by GPx2 reexpression or HIF1alpha inhibition [PMID: 35193955].

## Summary

The GPX2 gene encodes Glutathione Peroxidase 2, an enzyme that catalyzes the reduction of hydroperoxides, including hydrogen peroxide, using glutathione as a substrate [CS: 10]. This reaction is crucial for detoxifying reactive oxygen species (ROS) and protecting cells from oxidative damage [CS: 10]. GPX2 is predominantly expressed in the gastrointestinal tract and also in the liver and plays a role in maintaining cellular redox homeostasis [CS: 10]. In the kidneys, renal ischemia-reperfusion injury leads to increased GPX2 mRNA levels, indicating a response to oxidative stress, as GPX2 works to mitigate the elevated levels of ROS that accompany this injury by reducing hydroperoxides and preserving cell viability [CS: 8].

In conditions of oxidative stress or toxicity in the kidney, such as exposure to chemicals (chloroxylenol, borax, triclosan, and methylisothiazolinone) or under a selenium-deficient diet, GPX2 expression is alteredï¿½upregulated in the case of oxidative stress and toxicity [CS: 7]. This upregulation suggests a protective mechanism where increased GPX2 expression helps counteract the toxic effects by reducing the accumulation of hydroperoxides and therefore potentially limiting tissue damage and promoting cell survival [CS: 9]. Elevated GPX2 expression in selenium-deficient conditions suggests a cellular preservation mechanism where the enzyme's increased abundance compensates for the compromised activity due to the lower availability of its cofactor, selenium [CS: 7].
