| Full text | |
| Author(s): |
Truzzi, Daniela R.
[1]
;
Coelho, Fernando R.
[1]
;
Paviani, Veronica
[1]
;
Alves, Simone V.
[2]
;
Netto, Luis E. S.
[2]
;
Augusto, Ohara
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Av Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Journal of Biological Chemistry; v. 294, n. 38, p. 14055-14067, SEP 20 2019. |
| Web of Science Citations: | 3 |
| Abstract | |
2-Cys peroxiredoxins (Prxs) rapidly reduce H2O2, thereby acting as antioxidants and also as sensors and transmitters of H2O2 signals in cells. Interestingly, eukaryotic 2-Cys Prxs lose their peroxidase activity at high H2O2 levels. Under these conditions, H2O2 oxidizes the sulfenic acid derivative of the Prx peroxidatic Cys (CPSOH) to the sulfinate (CPSO2-) and sulfonated (CPSO3-) forms, redirecting the CPSOH intermediate from the catalytic cycle to the hyperoxidation/inactivation pathway. The susceptibility of 2-Cys Prxs to hyperoxidation varies greatly and depends on structural features that affect the life-time of the CPSOH intermediate. Among the human Prxs, Prx1 has an intermediate susceptibility to H2O2 and was selected here to investigate the effect of a physiological concentration of HCO3-/CO2 (25 mM) on its hyperoxidation. Immunoblotting and kinetic and MS/MS experiments revealed that HCO3-/CO2 increases Prx1 hyperoxidation and inactivation both in the presence of excess H2O2 and during enzymatic (NADPH/thioredoxin reductase/thioredoxin) and chemical (DTT) turnover. We hypothesized that the stimulating effect of HCO3-/CO2 was due to HCO4-, a peroxide present in equilibrated solutions of H2O2 and HCO3-/CO2. Indeed, additional experiments and calculations uncovered that HCO4- oxidizes CPSOH to CPSO2- with a second-order rate constant 2 orders of magnitude higher than that of H2O2 ((1.5 +/- 0.1) x 10(5) and (2.9 +/- 0.2) x 10(3) M-1.s(-1), respectively) and that HCO4- is 250 times more efficient than H2O2 at inactivating 1% Prx1 per turnover. The fact that the biologically ubiquitous HCO3-/CO2 pair stimulates Prx1 hyperoxidation and inactivation bears relevance to Prx1 functions beyond its antioxidant activity. (AU) | |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |