Sevoflurane inhibits ferroptosis: A new mechanism to explain its protective role against lipopolysaccharide-induced acute lung injury

Liu, Xiao; Wang, Ling; Xing, Qu; Li, Ke-Han; Si, Jianluo; Ma, Xiao-wu; Mao, Lianjing

doi:10.1016/j.lfs.2021.119391

Cited by 47 publications

(25 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we identified another function of Sev on suppressing glioma cell proliferation via activation of ferroptosis. Even though Sev was reported to inhibit ferroptosis and to exhibit a protective role against lipopolysaccharide-induced acute lung injury ( 33 ), the effect of Sev on ferroptosis of glioma cells was the first time to be illustrated in this study.…”

Section: Discussionmentioning

confidence: 86%

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Zhang

Chen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

ObjectiveTo clarify the function and mechanisms of sevoflurane (Sev) on ferroptosis in glioma cells.MethodsDifferent concentrations of Sev were used to treat glioma cells U87 and U251. Ferroptosis inducer Erastin was used to incubate glioma cells combined with Sev and ATF4 siRNA transfection treatment. CCK-8 assay and colorimetric assay were performed to analyze cell viability and Fe+ concentration, respectively. The releases of reactive oxygen species (ROS) were determined by flow cytometry analysis. Transcriptional sequencing was used to screen the differential genes affected by Sev in U251 cells. The mRNA and protein expression of ferroptosis-associated genes was detected by qRT-PCR and Western blotting.ResultsSev could suppress cell viability, increase ROS levels and Fe+ concentration, downregulate the protein expression levels of GPX4, and upregulate transferrin, ferritin, and Beclin-1 in a dose-dependent manner in U87 and U251 cells. The expression of ferroptosis and mitophagy-related gene activating transcription factor 4 (ATF4) was identified to be enhanced by Sev analyzed by transcriptional sequencing. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), which is involved in ferroptosis, is a downstream gene of ATF4. Inhibition of ATF4 could interrupt the expression of CHAC1 induced by Sev in U87 and U251 cells. Ferroptosis inducer Erastin treatment obviously inhibited the cell viability, elevated the Fe2+ concentration, and promoted ROS generation in U87 and U251 cells. The protein level of ATF4 and CHAC1 was increased in Erastin-treated U87 and U251 cells. Moreover, the interruption of Sev-induced ferroptosis and CHAC1 activating induced by ATF4 suppression could be reversed by Erastin.ConclusionsIn summary, this study suggested that Sev exposure-induced ferroptosis by the ATF4-CHAC1 pathway in glioma cells.

show abstract

Section: Discussionmentioning

confidence: 86%

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Zhang

Chen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…GSH is a crucial antioxidant and substrate for GPX4 to protect lipids from peroxidation [ 46 ]. Studies revealed that the augmentation of MDA and the reduction of GSH and tGPX4 contribute to lung damage and ALI [ 47 , 48 ]. Moreover, Nrf2 can exert a protective effect in ALI via reducing of MDA and increasing the contents of GSH and tGPX4 [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

Jiang

Liu

et al. 2021

IJMS

View full text Add to dashboard Cite

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

show abstract

“…HO-1 is a well-known intracellular enzyme, whose activation provides cyto-protective effects during acute inflammation, hypoxia, and hyperoxia [ 49 ]. Previous data suggested a possible link between sevoflurane and HO-1 expression [ 36 , 50 ]. First, we evaluated the impact of hemin and sevoflurane on HO-1 gene and protein expression.…”

Section: Resultsmentioning

confidence: 99%

Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1

Ngamsri¹,

Fuhr²,

Schindler³

et al. 2022

Cells

View full text Add to dashboard Cite

Acute respiratory distress syndrome is a life-threatening disease associated with high mortality. The adenosine receptor A2B (Adora2b) provides anti-inflammatory effects, which are also associated with the intracellular enzyme heme oxygenase-1 (HO-1). Our study determined the mechanism of sevoflurane’s protective properties and investigated the link between sevoflurane and the impact of a functional Adora2b via HO-1 modulation during lipopolysaccharide (LPS)-induced lung injury. We examined the LPS-induced infiltration of polymorphonuclear neutrophils (PMNs) into the lung tissue and protein extravasation in wild-type and Adora2b−/− animals. We generated chimeric animals, to identify the impact of sevoflurane on Adora2b of hematopoietic and non-hematopoietic cells. Sevoflurane decreased the LPS-induced PMN-infiltration and diminished the edema formation in wild-type mice. Reduced PMN counts after sevoflurane treatment were detected only in chimeric mice, which expressed Adora2b exclusively on leukocytes. The Adora2b on hematopoietic and non-hematopoietic cells was required to improve the permeability after sevoflurane inhalation. Further, sevoflurane increased the protective effects of HO-1 modulation on PMN migration and microvascular permeability. These protective effects were abrogated by specific HO-1 inhibition. In conclusion, our data revealed new insights into the protective mechanisms of sevoflurane application during acute pulmonary inflammation and the link between sevoflurane and Adora2b, and HO-1 signaling, respectively.

show abstract

Sevoflurane inhibits ferroptosis: A new mechanism to explain its protective role against lipopolysaccharide-induced acute lung injury

Cited by 47 publications

References 53 publications

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1

Contact Info

Product

Resources

About