Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury

Chen, Xueshi; Gao, Cheng; Yan, Ya'nan; Cheng, Zhiqi; Chen, Guang; Rui, Tongyu; Luo, Chengliang; Gao, Yuan; Wang, Tao; Chen, Xiping; Tao, Luyang

doi:10.1016/j.expneurol.2021.113762

Cited by 37 publications

(27 citation statements)

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“… 12 3F3-FMA, as well as other anti-TfR1 antibodies, exhibits an increase in total and membrane-localized fluorescence when used to stain cells undergoing ferroptosis in culture (compared to vehicle-treated control cells). TfR1 has been used to identify the occurrence of ferroptosis in traumatic brain injury 13 and myocardial ischemia/reperfusion injury, 14 among other uses. Thus, TfR1 serves as a biomarker to facilitate the identification of ferroptosis in cell and tissue contexts.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Classifies Ferroptosis and Apoptosis Cell Death Modalities with TfR1 Immunostaining

et al. 2022

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Determining cell death mechanisms occurring in patient and animal tissues is a longstanding goal that requires suitable biomarkers and accurate quantification. However, effective methods remain elusive. To develop more powerful and unbiased analytic frameworks, we developed a machine learning approach for automated cell death classification. Image sets were collected of HT-1080 fibrosarcoma cells undergoing ferroptosis or apoptosis and stained with an anti-transferrin receptor 1 (TfR1) antibody, together with nuclear and F-actin staining. Features were extracted using high-content-analysis software, and a classifier was constructed by fitting a multinomial logistic lasso regression model to the data. The prediction accuracy of the classifier within three classes (control, ferroptosis, apoptosis) was 93%. Thus, TfR1 staining, combined with nuclear and F-actin staining, can reliably detect both apoptotic and ferroptotis cells when cell features are analyzed in an unbiased manner using machine learning, providing a method for unbiased analysis of modes of cell death.

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Section: Introductionmentioning

confidence: 99%

Machine Learning Classifies Ferroptosis and Apoptosis Cell Death Modalities with TfR1 Immunostaining

et al. 2022

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“…In a previous study from our group [ 23 ], iron deposition was observed to increase 3–7 days after TBI in a mouse model. We [ 24 ] also found that iron deposition in the injured cortex was significantly higher than that in control cortex 21 days after TBI. Furthermore, we demonstrated that the iron metabolism pathway-related proteins TfR1, FPN, FTH, and FTL were temporally expressed in injured cortex, with TfR1 and FPN expression peaking 6–12 h after TBI and FTH and FTL expression peaking 3–7 days after TBI [ 23 , 24 ].…”

Section: The Ferroptosis Regulatory Pathway and Ferroptosis Activatio...mentioning

confidence: 91%

“…We [ 24 ] also found that iron deposition in the injured cortex was significantly higher than that in control cortex 21 days after TBI. Furthermore, we demonstrated that the iron metabolism pathway-related proteins TfR1, FPN, FTH, and FTL were temporally expressed in injured cortex, with TfR1 and FPN expression peaking 6–12 h after TBI and FTH and FTL expression peaking 3–7 days after TBI [ 23 , 24 ]. These findings suggest that the amount of iron deposition and expression of iron metabolism pathway-related proteins in the injured area correlate with the time since TBI.…”

Section: The Ferroptosis Regulatory Pathway and Ferroptosis Activatio...mentioning

confidence: 91%

Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

Pang

Zheng

Ren

et al. 2022

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI) is a serious health issue with a high incidence, high morbidity, and high mortality that poses a large burden on society. Further understanding of the pathophysiology and cell death models induced by TBI may support targeted therapies for TBI patients. Ferroptosis, a model of programmed cell death first defined in 2012, is characterized by iron dyshomeostasis, lipid peroxidation, and glutathione (GSH) depletion. Ferroptosis is distinct from apoptosis, autophagy, pyroptosis, and necroptosis and has been shown to play a role in secondary brain injury and worsen long-term outcomes after TBI. This review systematically describes (1) the regulatory pathways of ferroptosis after TBI, (2) the neurobiological links between ferroptosis and other cell death models, and (3) potential therapies targeting ferroptosis for TBI patients.

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“…MiR-212-5p attenuates neuronal ferroptosis after TBI by targeting PTGS2 [141]. Ruxolitinib was found to protect against neuronal ferroptosis in a mouse TBI model [142]. Ferristatin II, an iron uptake inhibitor, prevents neuronal ferroptosis after TBI [143], while tetrandrine ameliorates TBI by regulating autophagy to reduce ferroptosis [144].…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Ferroptosis and Its Role in Chronic Diseases

Liu

Zhu

et al. 2022

Cells

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Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of cell death. The course of ferroptosis can be accurately regulated by the metabolism of iron, lipids, amino acids, and various signal pathways. In this review, we summarize the basic characteristics of ferroptosis, its regulation, as well as the relationship between ferroptosis and chronic diseases such as cancer, nervous system diseases, metabolic diseases, and inflammatory bowel diseases. Finally, we describe the regulatory effects of food-borne active ingredients on ferroptosis.

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Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury

Cited by 37 publications

References 50 publications

Machine Learning Classifies Ferroptosis and Apoptosis Cell Death Modalities with TfR1 Immunostaining

Machine Learning Classifies Ferroptosis and Apoptosis Cell Death Modalities with TfR1 Immunostaining

Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

Ferroptosis and Its Role in Chronic Diseases

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