PMID- 35883901
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 7
DP  - 2022 Jul 21
TI  - Hydrogen Sulfide Donor GYY4137 Rescues NRF2 Activation in Respiratory Syncytial 
      Virus Infection.
LID - 10.3390/antiox11071410 [doi]
LID - 1410
AB  - Respiratory syncytial virus (RSV) can cause severe respiratory illness in 
      infants, immunocompromised, and older adults. Despite its burden, no vaccine or 
      specific treatment is available. RSV infection is associated with increased 
      reactive oxygen species (ROS) production, degradation of the transcription factor 
      nuclear factor erythroid 2-related factor 2 (NRF2), and decreased antioxidant 
      enzymes (AOEs), leading to oxidative damage and lung injury. Hydrogen sulfide 
      (H(2)S) is an endogenous gaseous molecule that plays a physiological role in 
      numerous cellular processes and a protective role in multiple pathological 
      conditions, displaying vasoactive, cytoprotective, anti-inflammatory, and 
      antioxidant activities. H(2)S can promote NRF2 activation through the 
      sulfhydration of Kelch-like ECH-associated protein 1, the cytoplasmic repressor 
      of NRF2. Here we investigated whether increasing cellular H(2)S levels could 
      rescue NRF2 and NRF2-dependent gene expression in RSV-infected primary airway 
      epithelial cells. We found that treatment with the H(2)S donor GYY4137 
      significantly increased NRF2 levels and AOEs gene expression by decreasing KEAP1 
      levels, and by modulating pathways involved in RSV-induced NRF2 degradation, such 
      as NRF2 ubiquitination, and promyelocytic leukemia (PML) protein levels. These 
      results suggest that the administration of exogenous H(2)S can positively impact 
      the altered redox balance associated with RSV infection, which represents an 
      important determinant of RSV-induced lung disease.
FAU - Haas de Mello, Aline
AU  - Haas de Mello A
AUID- ORCID: 0000-0002-5437-7191
AD  - Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 
      77555, USA.
FAU - Liu, Tianshuang
AU  - Liu T
AD  - Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 
      77555, USA.
FAU - Garofalo, Roberto P
AU  - Garofalo RP
AD  - Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 
      77555, USA.
AD  - Department of Microbiology and Immunology, The University of Texas Medical 
      Branch, Galveston, TX 77555, USA.
FAU - Casola, Antonella
AU  - Casola A
AD  - Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 
      77555, USA.
AD  - Department of Microbiology and Immunology, The University of Texas Medical 
      Branch, Galveston, TX 77555, USA.
LA  - eng
GR  - AI062885/NH/NIH HHS/United States
GR  - AI125434/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20220721
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC9311616
OTO - NOTNLM
OT  - GYY4137
OT  - H2S donor
OT  - NRF2
OT  - antioxidant enzymes
OT  - hydrogen sulfide
OT  - respiratory syncytial virus
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/21
CRDT- 2022/07/27 01:07
PHST- 2022/07/05 00:00 [received]
PHST- 2022/07/19 00:00 [revised]
PHST- 2022/07/20 00:00 [accepted]
PHST- 2022/07/27 01:07 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/21 00:00 [pmc-release]
AID - antiox11071410 [pii]
AID - antioxidants-11-01410 [pii]
AID - 10.3390/antiox11071410 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2022 Jul 21;11(7):1410. doi: 10.3390/antiox11071410.