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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Hughes, MM; Hooftman, A; Angiari, S; Tummala, P; Zaslona, Z; Runtsch, MC; McGettrick, AF; Sutton, CE; Diskin, C; Rooke, M; Takahashi, S; Sundararaj, S; Casarotto, MG; Dahlstrom, JE; Palsson-McDermott, EM; Corr, SC; Mills, KHG; Preston, RJS; Neamati, N; Xie, Y; Baell, JB; Board, PG; O'Neill, LAJ.
Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation.
Cell Rep. 2019; 29(1): 151-161.
Doi: 10.1016/j.celrep.2019.08.072
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- Co-authors Med Uni Graz
- Angiari Stefano
- Runtsch Marah
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- Abstract:
- The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1-/- mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cytokines - metabolism
- Glutathione Transferase - metabolism
- HEK293 Cells -
- Humans -
- Inflammasomes - metabolism
- Inflammation - metabolism
- Inflammation Mediators - metabolism
- Mice -
- Mice, Inbred C57BL -
- NIMA-Related Kinases - metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein - metabolism