PXD044043

PXD044043 is an original dataset announced via ProteomeXchange.

Title	Widespread cysteine persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress
Description	A hallmark of immune-inflammatory responses is the generation of reactive oxygen and nitrogen species by innate immune cells, in particular macrophages. How macrophages cope with excess oxidant production and associated redox stress is not fully understood. Recent evidence implicates reactive sulfur species (RSS) in inflammatory responses, however, how RSS affect macrophage function and its ability to cope with oxidative-inflammatory stress remains poorly understood. Herein, we investigated endogenous pathways of RSS biogenesis and clearance in macrophages, and in particular, explored how hydrogen sulfide (H2S) and thiol persulidation influences macrophage oxidative-inflammatory response. We report that classical activation of mouse or human macrophages with lipopolysaccharide and interferon-γ (LPS/IFN-γ) triggers a marked production of H2S/RSS, leading to a widespread increase in protein persulfidation. Endogenous H2S/persulfidation levels were governed by the activity of the cystine importer xCT, the H2S-generating enzyme cystathionine γ-lyase and the sulfide-metabolizing enzyme sulfide quinone oxidoreductase (SQOR). High levels of H2S/persulfidation, observed upon LPS/IFN-γ stimulation or SQOR inhibition, were associated with a state of increased resistance to oxidative stress. Furthermore, enhanced persulfidation correlated with attenuated activation of the macrophage inflammasome and diminished inflammatory cell death. These findings shed light on the metabolism and effects of RSS in macrophages and point to an important role for persulfides in enabling macrophages to cope with oxidative-inflammatory stress.
HostingRepository	PRIDE
AnnounceDate	2024-05-21
AnnouncementXML	Submission_2024-05-21_07:06:43.341.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-24 08:49:46	ID requested
⏵ 1	2024-05-21 07:06:44	announced

10.1016/j.redox.2024.103125;

Salti T, Braunstein I, Haimovich Y, Ziv T, Benhar M, Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress. Redox Biol, 72():103125(2024) [pubmed]

submitter keyword: oxidative-inflammatory stress, macrophages

Moran Benhar
contact affiliation	Department of Biochemistry, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, 31096, Israel
contact email	benhar@technion.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044043
     1. Label: PRIDE project
     2. Name: Widespread cysteine persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress