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The release and activity of HMGB1 in ferroptosis.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Mar 05; Vol. 510 (2), pp. 278-283. Date of Electronic Publication: 2019 Jan 25. - Publication Year :
- 2019
-
Abstract
- Damage-associated molecular pattern molecules (DAMPs) are endogenous danger signals that alert the innate immune system and shape the inflammation response to cell death. However, the release and activity of DAMPs in ferroptosis, a recently identified form of regulated necrosis characterized by iron overload and lipid peroxidation, still remain poorly understood. Here, we demonstrate that HMGB1 is a DAMP released by ferroptotic cells in an autophagy-dependent manner. Both type I and II ferroptosis activators, including erastin, sorafenib, RSL3, and FIN56, induce HMGB1 release in cancer and noncancer cells. In contrast, genetic ablation (using ATG5 <superscript>-/-</superscript> or ATG7 <superscript>-/-</superscript> cells) or pharmacologic inhibition (the administration of bafilomycin A1 or chloroquine) of autophagy was found to block ferroptosis activator-induced HMGB1 release. Mechanically, autophagy-mediated HDAC inhibition promotes HMGB1 acetylation, resulting in HMGB1 release in ferroptosis. Moreover, AGER, but not TLR4, is required for HMGB1-mediated inflammation in macrophages in response to ferroptotic cells. These studies suggest that HMGB1 inhibition might have some potential therapeutic effects in ferroptosis-associated human disease.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Carbolines pharmacology
Cell Line, Tumor
Chloroquine pharmacology
Ferritins metabolism
Fibroblasts metabolism
Humans
Immunity, Innate
Inflammation
Iron Overload
Lipid Peroxidation
Macrolides pharmacology
Mice
Neoplasms
Oximes pharmacology
Piperazines pharmacology
Sorafenib pharmacology
Sulfonamides pharmacology
Toll-Like Receptor 4 metabolism
Autophagy
Cell Death
HMGB1 Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 510
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 30686534
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.01.090