Crosstalk of pyroptosis, ferroptosis, and mitochondrial aldehyde dehydrogenase 2-related mechanisms in sepsis-induced lung injury in a mouse model

Cao, Zhenzhen; Qin, Hongqian; Huang, Yuhui; Zhao, Yong; Chen, Zhipeng; Hu, Jian; Gao, Qin

doi:10.1080/21655979.2022.2033381

Cited by 55 publications

(31 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro studies in mice have shown that ferroptosis can significantly reduce the proinflammatory cytokines secreted by macrophages induced by LPS, such as TNF- α , IL-6, and IL-8 [ 23 ]. Cao et al [ 24 ] found that ferroptosis can significantly inhibit IL-1 after LPS induced mouse bone marrow-derived macrophages β , TNF- α , and IL-6, thereby alleviating systemic inflammatory response. Zhang et al [ 25 ] confirmed that ferroptosis can reduce the inflammatory cytokine IL-1 in the mouse model β horizontal effect.…”

Section: Effect Of Ferroptosis On Anti-inflammatory Activity Of Macro...mentioning

confidence: 99%

Ferroptosis in Macrophage Impairment in Sepsis

Liu

2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

Sepsis is a clinical syndrome with high mortality, which can lead to multiple organ dysfunction syndrome. Nonspecific immune dysfunction and immune imbalance are its important pathological features. Macrophages are important immune cells and one of the important components of innate and adaptive immunity. Regulating the function of macrophages may be a potential method for the treatment of sepsis. Up to now, ferroptosis has been proved to be involved in the pathophysiological mechanism of many diseases, such as Alzheimer’s disease, cancer, Parkinson’s disease, and renal degeneration. At present, relevant studies have reported that ferroptosis may be involved in the occurrence of sepsis This paper reviews the existing mechanisms of iron ptosis in macrophages in sepsis, with a view to providing si’l for future studies on sepsis.

show abstract

Section: Effect Of Ferroptosis On Anti-inflammatory Activity Of Macro...mentioning

confidence: 99%

Ferroptosis in Macrophage Impairment in Sepsis

Liu

2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

show abstract

“…Of special note, changes in mitochondrial aldehyde dehydrogenase metabolism have been demonstrated at the crossroad of ferroptosis and pyroptosis signaling pathways [ 76 ]. Along the same line, Kang et al recently reported that the key ferroptosis regulator GPX4 also acts as a negative regulator of the pyroptotic cell death pathway [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response

et al. 2022

View full text Add to dashboard Cite

Despite recent advances in melanoma treatment, there are still patients that either do not respond or develop resistance. This unresponsiveness and/or acquired resistance to therapy could be explained by the fact that some melanoma cells reside in a dedifferentiated state. Interestingly, this dedifferentiated state is associated with greater sensitivity to ferroptosis, a lipid peroxidation-reliant, iron-dependent form of cell death. Cytoglobin (CYGB) is an iron hexacoordinated globin that is highly enriched in melanocytes and frequently downregulated during melanomagenesis. In this study, we investigated the potential effect of CYGB on the cellular sensitivity towards (1S, 3R)-RAS-selective lethal small molecule (RSL3)-mediated ferroptosis in the G361 melanoma cells with abundant endogenous expression. Our findings show that an increased basal ROS level and higher degree of lipid peroxidation upon RSL3 treatment contribute to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor-suppressive role for CYGB. Remarkably, CYGB knockdown also triggers activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and subsequent induction of pyroptosis target genes. Altogether, we show that silencing of CYGB expression modulates cancer therapy sensitivity via regulation of ferroptosis and pyroptosis cell death signaling pathways.

show abstract

“…In the setting of hypoxia-induced lung injury, Patil et al (15,16) demonstrated that Alda-1 treatment improved mitochondrial membrane potential and decreased oxidative stress and apoptosis in human lung vascular endothelial cells, and alleviated lung inflammation and oxidative stress and enhanced its cell survival via the Akt and mammalian target of rapamycin pathways in mice. In the setting of sepsis-induced lung injury, Cao et al (17) demonstrated that Alda-1 treatment simultaneously reduced lung pyroptosis and ferroptosis and therefore alleviated its injury in mice. In the setting of heatstroke-induced lung injury, Tsai et al (18) demonstrated that Alda-1 treatment attenuated lung injury through the reduction of reactive oxygen species and toxic aldehydes, and the alleviation of vascular inflammation and endothelial dysfunction in in vitro and in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

Alda-1 Treatment Alleviates Lung Injury After Cardiac Arrest and Resuscitation in Swine

Wu¹,

Xu²,

Diao

et al. 2022

Shock

View full text Add to dashboard Cite

Alda-1, an aldehyde dehydrogenase 2 (ALDH2) activator, has been shown to protect the lung against a variety of diseases including regional ischemia-reperfusion injury, severe hemorrhagic shock, hyperoxia, and so on. The present study was designed to investigate the effectiveness of Alda-1 treatment in alleviating lung injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in swine. Methods: A total of 24 swine were randomized into three groups: sham (n = 6), CA/CPR (n = 10), and CA/CPR + Alda-1 (n = 8). The swine model was established by 8 min of electrically induced and untreated CA, and then 8 min of manual CPR. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 min after CA/CPR. After CA/CPR, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) were regularly evaluated for 4 h. At 24 h after resuscitation, lung ALDH2 activity was detected, and its injury score, apoptosis, and ferroptosis were measured. Results: After experiencing the same procedure of CA and CPR, five swine in the CA/CPR group and six swine in the CA/CPR + Alda-1 group restored spontaneous circulation. Subsequently, significantly increased ELWI and PVPI, and markedly decreased OI were observed in these two groups compared with the sham group. However, all of them were gradually improved and significantly better in the swine treated with the Alda-1 compared with the CA/CPR group. Tissue analysis indicated that lung ALDH2 activity was significantly decreased in those swine experiencing the CA/ CPR procedure compared with the sham group; nevertheless, its activity was significantly greater in the CA/CPR + Alda-1 group than in the CA/CPR group. In addition, lung injury score, and its apoptosis and ferroptosis were significantly increased in the CA/ CPR and CA/CPR + Alda-1 groups compared with the sham group. Likewise, Alda-1 treatment significantly decreased these pathological damages in lung tissue when compared with the CA/CPR group. Conclusions: Alda-1 treatment was effective to alleviate lung injury after CA/CPR in a swine model, in which the protective role was possibly related to the inhibition of cell apoptosis and ferroptosis. It might provide a novel therapeutic target and a feasible therapeutic drug for lung protection after CA/CPR.

show abstract

Crosstalk of pyroptosis, ferroptosis, and mitochondrial aldehyde dehydrogenase 2-related mechanisms in sepsis-induced lung injury in a mouse model

Cited by 55 publications

References 34 publications

Ferroptosis in Macrophage Impairment in Sepsis

Ferroptosis in Macrophage Impairment in Sepsis

Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response

Alda-1 Treatment Alleviates Lung Injury After Cardiac Arrest and Resuscitation in Swine

Contact Info

Product

Resources

About