Journal
CELLULAR SIGNALLING
Volume 96, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2022.110363
Keywords
Quercetin; Sepsis; Lung Injury; Endoplasmic reticulum stress; SIRT1
Categories
Funding
- National Natural Science Founda-tion of China [82002033, 82172144]
- Hubei Provincial Natural Science Foundation [2020CFB199]
Ask authors/readers for more resources
This study found that quercetin can protect against sepsis-induced acute lung injury by suppressing endoplasmic reticulum stress and mitochondrial dysfunction. The protective effect is achieved through induction of the SIRT1/AMPK pathway and reduction of oxidative damage.
Endoplasmic reticulum (ER) stress and mitochondrial dysfunction play a pivotal role in the pathological process of sepsis-induced acute lung injury (ALI). Quercetin has been proved to exert anti-inflammation in ALI. This study aimed to explore the protection mechanism of quercetin against sepsis-induced ALI via suppressing ER stress and mitochondrial dysfunction. Cecal ligation and puncture (CLP) mouse model was established to mimic sepsis, and LPS was used to stimulate murine lung epithelial (MLE-12) cells. We observed that quercetin ameliorated pulmonary pathological lesion and oxidative damage in sepsis-induced mice. In LPS-stimulated MLE-12 cells, quercetin could inhibit the level of ER stress as evidenced by decreased mRNA expression of PDI, CHOP, GRP78, ATF6, PERK, IRE1 alpha and improve mitochondrial function, as presented by increased MMP, SOD level and reduced production of ROS, MDA. Meanwhile, transcriptome analysis revealed that quercetin upregulated SIRT1/AMPK mRNA expression. Furthermore, we used siRNA to knockdown SIRT1 in MLE-12 cells, and we found that SIRT1 knockdown could abrogate the quercetin-elicited antioxidation in vitro. Therefore, quercetin could protect against sepsis-induced ALI by suppressing oxidative stress-mediated ER stress and mitochondrial dysfunction via induction of the SIRT1/AMPK pathways.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available