Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery

Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 01/2007; 175(5):779-89. DOI: 10.1083/jcb.200606005
Source: PubMed

ABSTRACT Inactivation of eukaryotic 2-Cys peroxiredoxins (Prxs) by hyperoxidation has been proposed to promote accumulation of hydrogen peroxide (H2O2) for redox-dependent signaling events. We examined the oxidation and oligomeric states of PrxI and -II in epithelial cells during mitogenic signaling and in response to fluxes of H2O2. During normal mitogenic signaling, hyperoxidation of PrxI and -II was not detected. In contrast, H2O2-dependent cell cycle arrest was correlated with hyperoxidation of PrxII, which resulted in quantitative recruitment of approximately 66- and approximately 140-kD PrxII complexes into large filamentous oligomers. Expression of cyclin D1 and cell proliferation did not resume until PrxII-SO2H was reduced and native PrxII complexes were regenerated. Ectopic expression of PrxI or -II increased Prx-SO2H levels in response to oxidant exposure and failed to protect cells from arrest. We propose a model in which Prxs function as peroxide dosimeters in subcellular processes that involve redox cycling, with hyperoxidation controlling structural transitions that alert cells of perturbations in peroxide homeostasis.

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    ABSTRACT: Peroxiredoxins (Prxs) have a critical role in protecting cells against oxidative damage generated by reactive oxygen species (ROS). PrxI and PrxII are more than 90% homologous in their amino acid sequences, and both proteins reduce . In this study, an over-expression plasmid carrying PrxI was transfected into mouse embryonic fibroblasts (MEFs) to investigate potential compensatory relationships between PrxI and PrxII. ROS levels induced by oxidative stress were increased in MEFs as compared to wild-type MEFs. Moreover, exposure of MEFs to caused a reduction in cell viability of about 10%, and the proportion of cell death was increased compared to mock-treated MEFs. However, transient over-expression of PrxI in MEFs conferred increased resistance against the oxidative damage, as evidenced by increased cell viability and reduced intracellular ROS levels under stress conditions. The findings suggest that over-expressed PrxI can partly compensate for the loss of PrxII function in PrxII-deficient MEFs.
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    ABSTRACT: Banana Fusarium wilt is a soil-spread fungal disease caused by Fusarium oxysporum. In China, the main virulence fungi in banana are F. oxysporum race 1 (F1, weak virulence) and race 4 (F4, strong virulence). To date, no proteomic analyses have compared the two races, but the difference in virulence between F1 and F4 might result from their differentially expressed proteins. Here we report the first comparative proteomics of F1 and F4 cultured under various conditions, and finally identify 99 protein species, which represent 59 unique proteins. These proteins are mainly involved in carbohydrate metabolism, post-translational modification, energy production, and inorganic ion transport. Bioinformatics analysis indicated that among the 46 proteins identified from F4 were several enzymes that might be important for virulence. Reverse transcription PCR analysis of the genes for 15 of the 56 proteins revealed that their transcriptional patterns were similar to their protein expression patterns. Taken together, these data suggest that proteins involved in carbohydrate metabolism and ion transport may be important in the pathogenesis of banana Fusarium wilt. Some enzymes such as catalase-peroxidase, galactosidase and chitinase might contribute to the strong virulence of F4. Overexpression or knockout of the genes for the F4-specific proteins will help us to further understand the molecular mechanism of Fusarium-induced banana wilt.
    PLoS ONE 12/2014; 9(12):e113818. DOI:10.1371/journal.pone.0113818 · 3.53 Impact Factor

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