Back to Search
Start Over
Crosstalk of pyroptosis, ferroptosis, and mitochondrial aldehyde dehydrogenase 2-related mechanisms in sepsis-induced lung injury in a mouse model
- Source :
- Bioengineered. 13:4810-4820
- Publication Year :
- 2022
- Publisher :
- Informa UK Limited, 2022.
-
Abstract
- Acute lung injury (ALI) is a common complication of sepsis. Mitochondrial aldehyde dehydrogenase 2 (ALDH2), an enzyme involved in aldehyde metabolism, exerts a protective effect against sepsis. This study investigated the possible mechanisms underlying the roles of ALDH2, pyroptosis, and ferroptosis in sepsis-induced lung injury. A mouse model of sepsis-induced lung injury was established by cecal ligation and puncture (CLP); lung morphology was evaluated by calculation of lung coefficient, hematoxylin-eosin staining, and electron microscopy. Malondialdehyde (MDA), reactive oxygen species (ROS), and 4-hydroxy-2-nonenal (4-HNE) protein expression levels were used to detect the level of lipid oxidative stress. In addition, total iron was detected using an iron detection kit, and the expression of ferroptosis-related proteins (PTGS2, GPX4), pyroptosis-related proteins, and ALDH2 was examined using western blotting. To further examine the likely mechanisms, the ferroptosis inhibitor ferrostatin 1 (Fer-1), NLRP3 inflammasome inhibitor MCC950, and ALDH2 activator Alda-1 were added. CLP-treated mice exhibited destruction of lung tissue morphology, lipid peroxidation injury, iron content, and increased lung PTGS2 protein expression, accompanied by a decrease in GPX4 protein expression. CLP also downregulated ALDH2 expression and increased the expression of the NLRP3 inflammasome and pyroptosis-related proteins. These adverse effects of CLP were relieved by Alda-1, Fer-1, and MCC950 treatment. In conclusion, both pyroptosis and ferroptosis participate in CLP-induced ALI, and ALDH2 plays a protective role by reducing pyroptosis and ferroptosis. This study provides a scientific basis for the treatment of lung injury in sepsis.
- Subjects :
- Inflammasomes
Aldehyde Dehydrogenase, Mitochondrial
Iron
Acute Lung Injury
Bioengineering
General Medicine
Applied Microbiology and Biotechnology
Mice, Inbred C57BL
Disease Models, Animal
Mice
Cyclooxygenase 2
Sepsis
NLR Family, Pyrin Domain-Containing 3 Protein
Pyroptosis
Animals
Ferroptosis
Biotechnology
Subjects
Details
- ISSN :
- 21655987 and 21655979
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Bioengineered
- Accession number :
- edsair.doi.dedup.....3dc200a832abfa0703974a53e5161e0a