PMID- 36859435
OWN - NLM
STAT- MEDLINE
DCOM- 20230303
LR  - 20230419
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Mar 1
TI  - NLRX1 knockdown attenuates pro-apoptotic signaling and cell death in pulmonary 
      hyperoxic acute injury.
PG  - 3441
LID - 10.1038/s41598-023-28206-x [doi]
LID - 3441
AB  - Hyperoxia is frequently used for treating acute respiratory failure, but it can 
      cause acute lung injury. Nucleotide-binding domain and 
      leucine-rich-repeat-containing family member X1 (NLRX1) is localized in 
      mitochondria and involved in production of reactive oxygen species, inflammation, 
      and apoptosis, which are the features of hyperoxic acute lung injury (HALI). The 
      contribution of NLRX1 to HALI has not previously been addressed. Thus, to 
      investigate the role of NLRX1 in hyperoxia, we generated a murine model of HALI 
      in wild-type (WT) and NLRX1(-/-) mice by exposure to > 95% oxygen for 72 h. As a 
      result, NLRX1 expression was elevated in mice exposed to hyperoxia. In acute lung 
      injury, levels of inflammatory cells, protein leakage, cell cytotoxicity, and 
      pro-inflammatory cytokines were diminished in NLRX1(-/-) mice compared to WT 
      mice. In a survival test, NLRX1(-/-) mice showed reduced mortality under 
      hyperoxic conditions, and apoptotic cell death and caspase expression and 
      activity were also lower in NLRX1(-/-) mice. Furthermore, levels of the MAPK 
      signaling proteins ERK 1/2, JNK, and p38 were decreased in NLRX1-deficient mice 
      than in WT mice exposed to hyperoxia. The study shows that a genetic deficit in 
      NLRX1 can suppress hyperoxia-induced apoptosis, suggesting that NLRX1 acts as a 
      pivotal regulator of HALI.
CI  - (c) 2023. The Author(s).
FAU - Kim, Hye Rin
AU  - Kim HR
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Kim, Mi Na
AU  - Kim MN
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Kim, Eun Gyul
AU  - Kim EG
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Leem, Ji Su
AU  - Leem JS
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Baek, Seung Min
AU  - Baek SM
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Lee, Yu Jin
AU  - Lee YJ
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Kim, Kyung Won
AU  - Kim KW
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
FAU - Kang, Min-Jong
AU  - Kang MJ
AD  - Section of Rheumatology, Allergy and Immunology, Department of Internal Medicine, 
      Yale University School of Medicine, New Haven, CT, USA.
FAU - Song, Tae Won
AU  - Song TW
AD  - Department of Pediatrics, Ilsan Paik Hospital, Inje University College of 
      Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang, 10380, Korea. twsong@paik.ac.kr.
FAU - Sohn, Myung Hyun
AU  - Sohn MH
AD  - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for 
      Immunology and Immunological Diseases, Severance Biomedical Science Institute, 
      Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University 
      College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea. 
      mhsohn@yuhs.ac.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230301
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (NLRX1 protein, mouse)
RN  - 0 (Mitochondrial Proteins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Hyperoxia
MH  - Apoptosis
MH  - Cell Death
MH  - *Acute Lung Injury
MH  - Signal Transduction
MH  - Mitochondrial Proteins
PMC - PMC9975446
COIS- The authors declare no competing interests.
EDAT- 2023/03/02 06:00
MHDA- 2023/03/04 06:00
PMCR- 2023/03/01
CRDT- 2023/03/01 23:45
PHST- 2022/10/19 00:00 [received]
PHST- 2023/01/13 00:00 [accepted]
PHST- 2023/03/01 23:45 [entrez]
PHST- 2023/03/02 06:00 [pubmed]
PHST- 2023/03/04 06:00 [medline]
PHST- 2023/03/01 00:00 [pmc-release]
AID - 10.1038/s41598-023-28206-x [pii]
AID - 28206 [pii]
AID - 10.1038/s41598-023-28206-x [doi]
PST - epublish
SO  - Sci Rep. 2023 Mar 1;13(1):3441. doi: 10.1038/s41598-023-28206-x.