PMID- 38238472
OWN - NLM
STAT- MEDLINE
DCOM- 20240201
LR  - 20240201
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Jan 18
TI  - CPT1A as a potential therapeutic target for lipopolysaccharide-induced acute lung 
      injury in mice.
PG  - 1600
LID - 10.1038/s41598-024-52042-2 [doi]
LID - 1600
AB  - Acute lung injury (ALI) remains a high mortality rate with dramatic lung 
      inflammation and alveolar epithelial cell death. Although fatty acid beta-oxidation 
      (FAO) impairment has been implicated in the pathogenesis of ALI, whether 
      Carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme for FAO, 
      plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. Accordingly, 
      we focused on exploring the effect of CPT1A in the context of ALI and the 
      underlying mechanisms. We found that overexpression of CPT1A (AAV-CPT1A) 
      effectively alleviated lung injury by reduction of lung wet-to-dry ratio, 
      inflammatory cell infiltration, and protein levels in the BALF of ALI mice. 
      Meanwhile, AAV-CPT1A significantly lessened histopathological changes and several 
      cytokines' secretions. In contrast, blocking CPT1A with etomoxir augmented 
      inflammatory responses and lung injury in ALI mice. Furthermore, we found that 
      overexpression of CPT1A with lentivirus reduced the apoptosis rates of alveolar 
      epithelial cells and the expression of apoptosis-related proteins induced by LPS 
      in MLE12 cells, while etomoxir increased the apoptosis of MLE12 cells. 
      Overexpression of CPT1A prevented the drop in bioenergetics, palmitate oxidation, 
      and ATP levels. In conclusion, the results rendered CPT1A worthy of further 
      development into a pharmaceutical drug for the treatment of ALI.
CI  - (c) 2024. The Author(s).
FAU - Wang, Gui-Yun
AU  - Wang GY
AD  - Shandong Xiehe University, Jinan, 250109, Shandong, China.
FAU - Xu, Xia
AU  - Xu X
AD  - Shandong Xiehe University, Jinan, 250109, Shandong, China.
FAU - Xiong, Da-Yan
AU  - Xiong DY
AD  - Xiangya School of Nursing, Central South University, Changsha, 410013, Hunan, 
      China.
FAU - Deng, Lang
AU  - Deng L
AD  - Xiangya School of Nursing, Central South University, Changsha, 410013, Hunan, 
      China.
FAU - Liu, Wei
AU  - Liu W
AD  - Xiangya School of Nursing, Central South University, Changsha, 410013, Hunan, 
      China.
FAU - Huang, Xiao-Ting
AU  - Huang XT
AD  - Xiangya School of Nursing, Central South University, Changsha, 410013, Hunan, 
      China. xiaotinghuang0813@163.com.
LA  - eng
GR  - 82100084/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20240118
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - 0 (Epoxy Compounds)
RN  - MSB3DD2XP6 (etomoxir)
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.3.1.21 (CPT1B protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Acute Lung Injury/chemically induced/drug therapy/genetics
MH  - Carnitine O-Palmitoyltransferase/genetics/metabolism
MH  - *Epoxy Compounds
MH  - *Lipopolysaccharides/metabolism
MH  - Lung/pathology
PMC - PMC10796431
COIS- The authors declare no competing interests.
EDAT- 2024/01/19 00:42
MHDA- 2024/01/22 06:42
PMCR- 2024/01/18
CRDT- 2024/01/18 23:23
PHST- 2023/06/28 00:00 [received]
PHST- 2024/01/12 00:00 [accepted]
PHST- 2024/01/22 06:42 [medline]
PHST- 2024/01/19 00:42 [pubmed]
PHST- 2024/01/18 23:23 [entrez]
PHST- 2024/01/18 00:00 [pmc-release]
AID - 10.1038/s41598-024-52042-2 [pii]
AID - 52042 [pii]
AID - 10.1038/s41598-024-52042-2 [doi]
PST - epublish
SO  - Sci Rep. 2024 Jan 18;14(1):1600. doi: 10.1038/s41598-024-52042-2.