In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 33 ( 2014-08-19), p. 12043-12048
Abstract:
The catalytic cysteine of the typical 2-Cys Prx subfamily of peroxiredoxins is occasionally hyperoxidized to cysteine sulfinic acid during the peroxidase catalytic cycle. Sulfinic Prx (Prx–SO 2 H) is reduced back to the active form of the enzyme by sulfiredoxin. The abundance of Prx–SO 2 H was recently shown to oscillate with a period of ∼24 h in human red blood cells (RBCs). We have now investigated the molecular mechanism and physiological relevance of such oscillation in mouse RBCs. Poisoning of RBCs with CO abolished Prx–SO 2 H formation, implicating H 2 O 2 produced from hemoglobin autoxidation in Prx hyperoxidation. RBCs express the closely related PrxI and PrxII isoforms, and analysis of RBCs deficient in either isoform identified PrxII as the hyperoxidized Prx in these cells. Unexpectedly, RBCs from sulfiredoxin-deficient mice also exhibited circadian oscillation of Prx–SO 2 H. Analysis of the effects of protease inhibitors together with the observation that the purified 20S proteasome degraded PrxII–SO 2 H selectively over nonhyperoxidized PrxII suggested that the 20S proteasome is responsible for the decay phase of PrxII–SO 2 H oscillation. About 1% of total PrxII undergoes daily oscillation, resulting in a gradual loss of PrxII during the life span of RBCs. PrxII–SO 2 H was detected in cytosolic and ghost membrane fractions of RBCs, and the amount of membrane-bound PrxII–SO 2 H oscillated in a phase opposite to that of total PrxII–SO 2 H. Our results suggest that membrane association of PrxII–SO 2 H is a tightly controlled process and might play a role in the tuning of RBC function to environmental changes.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1401100111
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2014
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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