| Full text | |
| Author(s): |
de Souza, Luiz F.
[1]
;
Pearson, Andree G.
[2]
;
Pace, Paul E.
[2]
;
Dafre, Alcir L.
[3]
;
Hampton, Mark B.
[2]
;
Meotti, Flavia C.
[1]
;
Winterbourn, Christine C.
[2]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Quim IQUSP, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Otago Christchurch, Dept Pathol & Biomed Sci, Ctr Free Rad Res, POB 4345, Christchurch 8040 - New Zealand
[3] Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Bioquim, BR-88040900 Florianopolis, SC - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Free Radical Biology and Medicine; v. 135, p. 227-234, MAY 1 2019. |
| Web of Science Citations: | 1 |
| Abstract | |
Peroxiredoxins (Prxs) are thiol peroxidases with a key role in antioxidant defense and redox signaling. They could be important in neutrophils for handling the large amount of oxidants that these cells produce. We investigated the redox state of Prx1 and Prx2 in HL-60 promyelocytic cells differentiated to neutrophil-like cells (dHL-60) and in human neutrophils. HL-60 cell differentiation with dimethyl sulfoxide caused a large decrease in expression of both Prxs, and all-trans retinoic acid also decreased Prx1 expression. Prx1 was mostly reduced in dHL-60 cells. NADPH oxidase activation by phorbol myristate acetate (PMA) or ingestion of Staphylococcus aureus induced rapid oxidation to disulfide-linked dimers, and eventually hyperoxidation. The NADPH oxidase inhibitor, diphenyleneiodonium, prevented Prx1 dimerization in stimulated dHL-60 cells, and decreased the extent of oxidation under resting conditions. In contrast, Prx1 and Prx2 were present in neutrophils from human blood as disulfides, and PMA or S. aureus caused no further oxidation. They remained oxidized on incubation with diphenyleneiodonium in media. Although this suggests that Prx redox cycling could be deficient in neutrophils, thioredoxin expression and thioredoxin reductase activity were similar in neutrophils and dHL-60 cells. Additionally, neutrophil thioredoxin was initially reduced and underwent oxidation after PMA activation. Thus, although the Prxs respond to oxidant generation in dHL-60 cells, in neutrophils they appear ``locked{''} as disulfides. On this basis we propose that neutrophil Prxs are inefficient antioxidants and contribute little to peroxide removal during the oxidative burst, and speculate that they might be involved in other cell processes. (AU) | |
| FAPESP's process: | 17/12312-8 - Role of Peroxiredoxins in the differentiation of myeloid leukemia cells and neutrophil function |
| Grantee: | Luiz Felipe de Souza |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |