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Peroxiredoxin-mediated disulfide bond formation is required for nucleocytoplasmic translocation and secretion of HMGB1 in response to inflammatory stimuli

Authors
 Man Sup Kwak  ;  Hee Sue Kim  ;  Khulan Lkhamsuren  ;  Young Hun Kim  ;  Myeong Gil Han  ;  Jae Min Shin  ;  In Ho Park  ;  Woo Joong Rhee  ;  Se Kyoung Lee  ;  Sue Goo Rhee  ;  Jeon-Soo Shin 
Citation
 REDOX BIOLOGY, Vol.24 : 101203, 2019 
Journal Title
 REDOX BIOLOGY 
Issue Date
2019
Keywords
H(2)O(2) ;  HMGB1 ; Oxidation ; Peroxiredoxin ;  Secretion
Abstract
The nuclear protein HMGB1 (high mobility group box 1) is secreted by monocytes-macrophages in response to inflammatory stimuli and serves as a danger-associated molecular pattern. Acetylation and phosphorylation of HMGB1 are implicated in the regulation of its nucleocytoplasmic translocation for secretion, although inflammatory stimuli are known to induce H2O2 production. Here we show that H2O2-induced oxidation of HMGB1, which results in the formation of an intramolecular disulfide bond between Cys23 and Cys45, is necessary and sufficient for its nucleocytoplasmic translocation and secretion. The oxidation is catalyzed by peroxiredoxin I (PrxI) and PrxII, which are first oxidized by H2O2 and then transfer their disulfide oxidation state to HMGB1. The disulfide form of HMGB1 showed higher affinity for nuclear exportin CRM1 compared with the reduced form. Lipopolysaccharide (LPS)-induced HMGB1 secretion was greatly attenuated in macrophages derived from PrxI or PrxII knockout mice, as was the LPS-induced increase in serum HMGB1 levels.
Files in This Item:
T201902251.pdf Download
DOI
10.1016/j.redox.2019.101203
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kwak, Man Sup(곽만섭) ORCID logo https://orcid.org/0000-0002-3989-3016
Park, Inho(박인호) ORCID logo https://orcid.org/0000-0003-2190-5469
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Rhee, Sue Goo(이서구)
Lee, Se Kyoung(이세경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170421
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