Abstract
Peroxiredoxins (Prxd) are key players in the control of redox homeostasis in the cell, both by its peroxidase activity and its role in redox signaling. We previously found that Prxd1 and Prxd2 expression drastically decreases upon myeloid cell differentiation (de Souza et al., 2019). Likewise, other groups have reported that Prxd inhibition diminishes myeloid cell proliferation. In this study we tried to understand the early events related to redox modulation and signaling that may lead to myeloid cell differentiation. Incubation of human leukemic-60 (HL-60) cells with 1 μM retinoic acid or 1.3% DMSO did not lead to significant Prxd 1 or 2 oxidation within 24h. Conversely, there was a decrease in HyPer7 probe oxidation 4h after incubation, which was accompanied by an increase in glutathione synthesis, suggesting an overall enhanced antioxidant status. A peak in Nrf-2 migration to the nucleus was found 4 and 8h after DMSO treatment, with an increase in the transcription of HO-1, δ-GCL, NQO-1. Paradoxically, the knockdown of Prxd 2 did not promote any differentiation, indicating that Prxd 2 suppression is a consequence rather than a cause for HL-60 differentiation. Immunoprecipitation of Prxd 2 followed by proteomics revealed Prxd 2 interaction with proteins involved in RNA processing and formation of stress granules, such as G3BP1, eIF4a and eEF1A. Interaction between G3BP1 and Prx2 was further confirmed by western blot and cell image. It occurs in naïve HL-60 and HeLa cells, but it is even more evident in stress granules induced by sodium arsenite. These results suggest that Prxd might be important to maintain cell homeostasis depending on RNA metabolism and stress granules formation.