2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications

Abstract

H(2)O(2) is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel peroxidase family that catalyze the H(2)O(2) reduction reaction in the presence of thioredoxin, thioredoxin reductase and NADPH. Several lines of evidence suggest that 2-Cys peroxiredoxins have dual roles as regulators of the H(2)O(2) signal and as defenders of oxidative stress. In particular, 2-Cys peroxiredoxin appears to provide selective, specific and localized control of receptor-mediated signal transduction. Thus, the therapeutic potential of 2-Cys peroxiredoxins is clear for diseases, such as cancer and cardiovascular diseases, that involve reactive oxygen species.

Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies

“…Elevated expression of major regulators of ROS signaling, such as Prxs and Trxs, has been identified in a wide range of human cancers (41). Using a tissue microarray, we showed that Srx was expressed in some basal cells of normal skin epidermis.…”

Human Umbilical Cord Blood Cells Protect Oligodendrocytes from Brain Ischemia through Akt Signal Transduction

“…Prdx4 is a secreted protein that has been reported to reduce extracellular oxidative stress (20) through peroxidase activity (43) and also serves as a chaperone that functions to prevent intracellular protein aggregation and subsequent apoptosis (44,45). Addition of this protein to human myeloid cells results in the activation of NF-B and a subsequent increase in the expression of its known target genes, Icam-1 and iNOS (36).…”

Oxidation of proteins: Basic principles and perspectives for blood proteomics

“…It was hypothesised that catalase and peroxiredoxin play complementary roles in H 2 O 2 detoxification/ signalling due to the different recycling mechanisms used [154]; in RBCs, peroxiredoxin 2 was shown to accumulate as a dimer under H 2 O 2 challenge, which was only slowly converted back to the active monomer by the thioredoxin system. This behaviour makes peroxiredoxin 2 ideally suited to H 2 O 2 sensing at low concentration [155]. When H 2 O 2 concentration increases, catalase and glutathione peroxidase are necessary to dispose of excess H 2 O 2 [156].…”