A pharmacological probe identifies cystathionine β-synthase as a new negative regulator for ferroptosis

Wang, Li; Cai, Hao; Hu, Yijun; Liu, Fan; Huang, Shan; Zhou, Yuwei; Yu, Jing; Xu, Jinyi; Wu, Fang

doi:10.1038/s41419-018-1063-2

Cited by 100 publications

(94 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is accompanied by elevated levels of the cysteine precursor homocysteine in plasma, generating a mouse model for severe homocystinuria [97,98]. Interestingly, a recently developed CBS inhibitor has been identified to induce ferroptosis in different cancer cell lines [99]. Yet, whether any aspect of the Cbs KO phenotype is related to overt induction of ferroptosis is unknown.…”

Section: In Vivo Relevance Of Ferroptosis: Lessons Learned From Knockmentioning

confidence: 99%

Ferroptosis in Cancer Cell Biology

Bebber

Müller

Clemente

et al. 2020

Cancers

250

209

View full text Add to dashboard Cite

A major hallmark of cancer is successful evasion of regulated forms of cell death. Ferroptosis is a recently discovered type of regulated necrosis which, unlike apoptosis or necroptosis, is independent of caspase activity and receptor-interacting protein 1 (RIPK1) kinase activity. Instead, ferroptotic cells die following iron-dependent lipid peroxidation, a process which is antagonised by glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1). Importantly, tumour cells escaping other forms of cell death have been suggested to maintain or acquire sensitivity to ferroptosis. Therefore, therapeutic exploitation of ferroptosis in cancer has received increasing attention. Here, we systematically review current literature on ferroptosis signalling, cross-signalling to cellular metabolism in cancer and a potential role for ferroptosis in tumour suppression and tumour immunology. By summarising current findings on cell biology relevant to ferroptosis in cancer, we aim to point out new conceptual avenues for utilising ferroptosis in systemic treatment approaches for cancer.

show abstract

Section: In Vivo Relevance Of Ferroptosis: Lessons Learned From Knockmentioning

confidence: 99%

Ferroptosis in Cancer Cell Biology

Bebber

Müller

Clemente

et al. 2020

Cancers

250

209

View full text Add to dashboard Cite

show abstract

“…Although the pathogenetic role of ferroptosis in ALI induced by seawater drowning is still elusive, its involvement in multiple human diseases has been established. Nowadays, ferroptosis has been recognized as a key mechanism for cell death associated with ischemic organ injury, neurodegeneration and cancer [15][16][17]. Ferroptosis induced by GPX4 inhibition could prevent cancer resistant to chemotherapy [18,19].…”

Section: Introductionmentioning

confidence: 99%

Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

Qiu

Wan

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Ferroptosis is a new type of nonapoptotic cell death model that was closely related to ROS accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.Methods: we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results: Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. These findings may guide the development of a new therapeutic approach for seawater drowning-induced ALI Conclusions: These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.

show abstract

“…The results showed that seawater exposure changed MLE-12 morphology ( Figure 1A) and decreased cellular viability in time-dependent manner ( Figure 1B). The results of ow cytometry detection of death also showed an increase in the proportion of cell death as the seawater exposure time prolonged ( Figure 1C and D) (17). These results indicate that seawater exposure caused MLE-12 cell damage and death.…”

Section: Seawater Exposure Induced Ferroptosis In Mle-12 Cellsmentioning

confidence: 62%

“…Beijing Cowin Biotech Co., Ltd., China) according to the manufacturer's instructions(17). The assay for lipid ROS was performed by incubating the cells for 1 hour at a nal concentration of 2 μM of BODIPY 581/591 C11 (Invitrogen) at 37 ℃.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

Qiu

Wan

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.Methods: we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms.Results: Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning.Conclusions: These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.

show abstract

A pharmacological probe identifies cystathionine β-synthase as a new negative regulator for ferroptosis

Cited by 100 publications

References 56 publications

Ferroptosis in Cancer Cell Biology

Ferroptosis in Cancer Cell Biology

Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

Contact Info

Product

Resources

About