PMID- 31847346
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 8
IP  - 12
DP  - 2019 Dec 14
TI  - Erastin Inhibits Septic Shock and Inflammatory Gene Expression via Suppression of 
      the NF-kappaB Pathway.
LID - 10.3390/jcm8122210 [doi]
LID - 2210
AB  - Sepsis is a life-threatening condition that is caused by an abnormal immune 
      response to infection and can lead to tissue damage, organ failure, and death. 
      Erastin is a small molecule capable of initiating ferroptotic cell death in 
      cancer cells. However, the function of erastin in the inflammatory response 
      during sepsis remains unknown. Here, we showed that erastin ameliorates septic 
      shock induced by cecal ligation and puncture or lipopolysaccharides (LPS) in 
      mice, which was associated with a reduced production of inflammatory mediators 
      such as nitric oxide, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. 
      Pretreatment with erastin in bone marrow-derived macrophages (BMDMs) 
      significantly attenuated the expression of inducible nitric oxide synthase, 
      cyclooxygenase-2, TNF-alpha, and IL-1beta mRNA in response to LPS treatment. 
      Furthermore, we also showed that erastin suppresses phosphorylation of IkappaB kinase 
      beta, phosphorylation and degradation of IkappaBalpha, and nuclear translocation of nuclear 
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) in LPS-stimulated 
      BMDMs. Our findings suggest that erastin attenuates the inflammatory response by 
      suppressing the NF-kappaB signaling pathway, resulting in inhibition of sepsis 
      development. This study provides new insights regarding the potential therapeutic 
      properties of erastin in sepsis.
FAU - Oh, Byung Moo
AU  - Oh BM
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
FAU - Lee, Seon-Jin
AU  - Lee SJ
AD  - Environmental Disease Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
AD  - Department of Biomolecular Science, KRIBB School of Bioscience, Korea University 
      of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea.
FAU - Park, Gyoung Lim
AU  - Park GL
AD  - Environmental Disease Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
AD  - Department of Biomolecular Science, KRIBB School of Bioscience, Korea University 
      of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea.
FAU - Hwang, Yo Sep
AU  - Hwang YS
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
AD  - Department of Biomolecular Science, KRIBB School of Bioscience, Korea University 
      of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea.
FAU - Lim, Jeewon
AU  - Lim J
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
AD  - Department of Biomolecular Science, KRIBB School of Bioscience, Korea University 
      of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea.
FAU - Park, Eun Sun
AU  - Park ES
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
AD  - Department of Biomolecular Science, KRIBB School of Bioscience, Korea University 
      of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea.
FAU - Lee, Kyung Ho
AU  - Lee KH
AD  - Anticancer Agent Research Center, Korea Research Institute of Bioscience and 
      Biotechnology (KRIBB), Cheongju 28116, Korea.
FAU - Kim, Bo Yeon
AU  - Kim BY
AD  - Anticancer Agent Research Center, Korea Research Institute of Bioscience and 
      Biotechnology (KRIBB), Cheongju 28116, Korea.
FAU - Kwon, Yong Tae
AU  - Kwon YT
AD  - Protein Metabolism Medical Research Center and Department of Biomedical Sciences, 
      College of Medicine, Seoul National University, Seoul 110-799, Korea.
FAU - Cho, Hee Jun
AU  - Cho HJ
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
FAU - Lee, Hee Gu
AU  - Lee HG
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Yuseong-gu, Daejeon 34141, Korea.
AD  - Department of Biomolecular Science, KRIBB School of Bioscience, Korea University 
      of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea.
LA  - eng
GR  - 2017R1A2B2005629/National Research Foundation of Korea/
GR  - CAP-16-03-KRIBB/R&D Convergence Program/
PT  - Journal Article
DEP - 20191214
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC6947339
OTO - NOTNLM
OT  - NF-kappaB
OT  - erastin
OT  - ferroptosis
OT  - inflammation
OT  - sepsis
COIS- The authors declare no conflict of interest.
EDAT- 2019/12/19 06:00
MHDA- 2019/12/19 06:01
PMCR- 2019/12/14
CRDT- 2019/12/19 06:00
PHST- 2019/11/21 00:00 [received]
PHST- 2019/12/06 00:00 [revised]
PHST- 2019/12/10 00:00 [accepted]
PHST- 2019/12/19 06:00 [entrez]
PHST- 2019/12/19 06:00 [pubmed]
PHST- 2019/12/19 06:01 [medline]
PHST- 2019/12/14 00:00 [pmc-release]
AID - jcm8122210 [pii]
AID - jcm-08-02210 [pii]
AID - 10.3390/jcm8122210 [doi]
PST - epublish
SO  - J Clin Med. 2019 Dec 14;8(12):2210. doi: 10.3390/jcm8122210.