Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells

Chun Seok Cho, Hyun Ju Yoon, Jeong Yeon Kim, Hyun Ae Woo, Sue Goo Rhee

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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-SO2H) is reduced back to the active form of the enzyme by sulfiredoxin. The abundance of Prx-SO2H 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-SO2H formation, implicating H2O2 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-SO2H. Analysis of the effects of protease inhibitors together with the observation that the purified 20S proteasome degraded PrxII-SO2H selectively over nonhyperoxidized PrxII suggested that the 20S proteasome is responsible for the decay phase of PrxII-SO 2H oscillation. About 1% of total PrxII undergoes daily oscillation, resulting in a gradual loss of PrxII during the life span of RBCs. PrxII-SO 2H was detected in cytosolic and ghost membrane fractions of RBCs, and the amount of membrane-bound PrxII-SO2H oscillated in a phase opposite to that of total PrxII-SO2H. Our results suggest that membrane association of PrxII-SO2H is a tightly controlled process and might play a role in the tuning of RBC function to environmental changes.

Original languageEnglish
Pages (from-to)12043-12048
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number33
DOIs
StatePublished - 19 Aug 2014

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