Enhanced hyperoxidation of peroxiredoxin 2 and peroxiredoxin 3 in the presence of bicarbonate/CO2

Hydrogen peroxide undergoes an equilibrium reaction with bicarbonate/CO2 to produce peroxymonocarbonate (HCO4-). Peroxymonocarbonate is more reactive with thiols than H2O2 but it makes up only a small fraction of the H2O2 in physiological bicarbonate buffers so the increase in rate of oxidation of l...

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Bibliographic Details
Published in:Free radical biology & medicine 2019-12, Vol.145, p.1-7
Main Authors: Peskin, Alexander V., Pace, Paul E., Winterbourn, Christine C.
Format: Article
Language:English
Subjects:
Bicarbonate
Hydrogen peroxide
Peroxiredoxin
Peroxymonocarbonate
Redox regulation
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Summary:Hydrogen peroxide undergoes an equilibrium reaction with bicarbonate/CO2 to produce peroxymonocarbonate (HCO4-). Peroxymonocarbonate is more reactive with thiols than H2O2 but it makes up only a small fraction of the H2O2 in physiological bicarbonate buffers so the increase in rate of oxidation of low molecular weight thiols is modest. However, for some thiol proteins such as protein tyrosine phosphatases, the rate enhancement is very much greater. We have investigated the effect of bicarbonate/CO2 on the oxidation of peroxiredoxins (Prdxs) 2 and 3. Using an assay in which reduced Prdx2 inhibits oxidation of horseradish peroxidase by H2O2, we saw no difference between phosphate and bicarbonate buffers (pH 7.4). However, hyperoxidation of both Prdxs in bicarbonate was considerably enhanced. Hyperoxidation involves the reaction of the sulfenic acid formed at the active site with a second H2O2, and prevents its condensation to a disulfide. Using LC/MS analysis, we determined that the presence of 25 mM bicarbonate/CO2 increased the ratio of hyperoxidation compared with condensation 6-fold for Prdx2 and 11-fold for Prdx3. These results imply that Prdx hyperoxidation will occur more readily under physiological conditions than appreciated from in vitro experiments, which seldom use bicarbonate buffers. They also raise the possibility that variations in bicarbonate concentration could provide a mechanism for regulating the cellular level of active Prdxs. [Display omitted] •Excess H2O2 causes hyperoxidation of mammalian 2Cys peroxiredoxins.•Prdx2 and Prxd3 are more readily hyperoxidized in presence of CO2/bicarbonate.•Peroxymonocarbonate formed in equilibrium with H2O2 can account for enhancement.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2019.09.010