Peroxiredoxin 2 functions as a noncatalytic scavenger of low-level hydrogen peroxide in the erythrocyte.

Abstract:

:Peroxiredoxin 2 (Prx2), a thiol-dependent peroxidase, is the third most abundant protein in the erythrocyte, and its absence in knock-out mice gives rise to hemolytic anemia. We have found that in human erythrocytes, Prx2 was extremely sensitive to oxidation by H(2)O(2), as dimerization was observed after exposure of 5 x 10(6) cells/mL to 0.5 muM H(2)O(2). In contrast to Prx2 in Jurkat T lymphocytes, Prx2 was resistant to overoxidation (oxidation of the cysteine thiol to a sulfinic/sulfonic acid) in erythrocytes. Reduction of dimerized Prx2 in the erythrocyte occurred very slowly, with reversal occurring gradually over a 20-minute period. Very low thioredoxin reductase activity was detected in hemolysates. We postulate that this limits the rate of Prx2 regeneration, and this inefficiency in recycling prevents the overoxidation of Prx2. We also found that Prx2 was oxidized by endogenously generated H(2)O(2), which was mainly derived from hemoglobin autoxidation. Our results demonstrate that in the erythrocyte Prx2 is extremely efficient at scavenging H(2)O(2) noncatalytically. Although it does not act as a classical antioxidant enzyme, its high concentration and substrate sensitivity enable it to handle low H(2)O(2) concentrations efficiently. These unique redox properties may account for its nonredundant role in erythrocyte defense against oxidative stress.

journal_name

Blood

journal_title

Blood

authors

Low FM,Hampton MB,Peskin AV,Winterbourn CC

doi

10.1182/blood-2006-09-048728

subject

Has Abstract

pub_date

2007-03-15 00:00:00

pages

2611-7

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2006-09-048728

journal_volume

109

pub_type

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