TY - JOUR
T1 - Nuclear heat shock protein 72 as a negative regulator of oxidative stress (hydrogen peroxide)-induced HMGB1 cytoplasmic translocation and release
AU - Tang, Daolin
AU - Kang, Rui
AU - Xiao, Weimin
AU - Jiang, Lei
AU - Liu, Meidong
AU - Shi, Yongzhong
AU - Wang, Kangkai
AU - Wang, Haichao
AU - Xiao, Xianzhong
PY - 2007/6/1
Y1 - 2007/6/1
N2 - In response to inflammatory stimuli (e.g., endotoxin, proinflammatory cytokines) or oxidative stress, macrophages actively release a ubiquitous nuclear protein, high-mobility group box 1 (HMGB1), to sustain an inflammatory response to infection or injury. In this study, we demonstrated mild heat shock (e.g., 42.5°C, 1 h), or enhanced expression of heat shock protein (Hsp) 72 (by gene transfection) similarly rendered macrophages resistant to oxidative stress-induced HMGB1 cytoplasmic translocation and release. In response to oxidative stress, cytoplasmic Hsp72 translocated to the nucleus, where it interacted with nuclear proteins including HMGB1. Genetic deletion of the nuclear localization sequence (NLS) or the peptide binding domain (PBD) from Hsp72 abolished oxidative stress-induced nuclear translocation of Hsp72-ΔNLS (but not Hsp72-ΔPBD), and prevented oxidative stress-induced Hsp72-ΔPBD-HMGB1 interaction in the nucleus. Furthermore, impairment of Hsp72-ΔNLS nuclear translocation, or Hsp72-ΔPBD-HMGB1 interaction in the nucleus, abrogated Hsp72-mediated suppression of HMGB1 cytoplasmic translocation and release. Taken together, these experimental data support a novel role for nuclear Hsp72 as a negative regulator of oxidative stress-induced HMGB1 cytoplasmic translocation and release.
AB - In response to inflammatory stimuli (e.g., endotoxin, proinflammatory cytokines) or oxidative stress, macrophages actively release a ubiquitous nuclear protein, high-mobility group box 1 (HMGB1), to sustain an inflammatory response to infection or injury. In this study, we demonstrated mild heat shock (e.g., 42.5°C, 1 h), or enhanced expression of heat shock protein (Hsp) 72 (by gene transfection) similarly rendered macrophages resistant to oxidative stress-induced HMGB1 cytoplasmic translocation and release. In response to oxidative stress, cytoplasmic Hsp72 translocated to the nucleus, where it interacted with nuclear proteins including HMGB1. Genetic deletion of the nuclear localization sequence (NLS) or the peptide binding domain (PBD) from Hsp72 abolished oxidative stress-induced nuclear translocation of Hsp72-ΔNLS (but not Hsp72-ΔPBD), and prevented oxidative stress-induced Hsp72-ΔPBD-HMGB1 interaction in the nucleus. Furthermore, impairment of Hsp72-ΔNLS nuclear translocation, or Hsp72-ΔPBD-HMGB1 interaction in the nucleus, abrogated Hsp72-mediated suppression of HMGB1 cytoplasmic translocation and release. Taken together, these experimental data support a novel role for nuclear Hsp72 as a negative regulator of oxidative stress-induced HMGB1 cytoplasmic translocation and release.
UR - http://www.scopus.com/inward/record.url?scp=34249779532&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249779532&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.178.11.7376
DO - 10.4049/jimmunol.178.11.7376
M3 - Article
C2 - 17513788
AN - SCOPUS:34249779532
SN - 0022-1767
VL - 178
SP - 7376
EP - 7384
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -