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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 proteinHMGB1(high mobility group box 1) is secreted by monocytes-macrophages inresponsetoinflammatorystimuliand serves as a danger-associated molecular pattern. Acetylation and phosphorylation ofHMGB1are implicated in the regulation of itsnucleocytoplasmictranslocationforsecretion, althoughinflammatorystimuliare known to induce H2O2production. Here we show that H2O2-induced oxidation ofHMGB1, which results in theformationof an intramoleculardisulfidebondbetween Cys23and Cys45, is necessary and sufficient for itsnucleocytoplasmictranslocationandsecretion. The oxidation is catalyzed by peroxiredoxin I (PrxI) and PrxII, which are first oxidized by H2O2and then transfer theirdisulfideoxidation state toHMGB1. Thedisulfideform ofHMGB1showed higher affinity for nuclear exportin CRM1 compared with the reduced form. Lipopolysaccharide (LPS)-inducedHMGB1secretionwas greatly attenuated in macrophages derived from PrxI or PrxII knockout mice, as was the LPS-induced increase in serumHMGB1levels.
Files in This Item:
T201902251.pdf Download
DOI
10.1016/j.redox.2019.101203
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 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)
Rhee, Woo Joong(이우중) ORCID logo https://orcid.org/0000-0001-9690-0553
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170421
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