Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00153)
Name
Neurotoxicity
ICD
ICD-11: NE61
Full List of Target(s) of This Ferroptosis-centered Disease
Diamine acetyltransferase 1 (SAT1)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Driver
Responsed Disease Sevoflurane induced neurotoxicity [ICD-11: NE61]
Responsed Drug Sevoflurane Approved
 Drug Info 
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously.

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Response regulation Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity.
Unspecific Target
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Sevoflurane induced neurotoxicity [ICD-11: NE61]
Responsed Drug Sevoflurane Approved
 Drug Info 
Responsed Regulator Serine-protein kinase ATM (ATM) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hBCs (Brain cells)
In Vivo Model
Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously.

    Click to Show/Hide
Response regulation Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity.
Sodium-coupled neutral amino acid symporter 1 (SLC38A1)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Formaldehyde-induced neurotoxicity [ICD-11: NE61]
Responsed Drug Formaldehyde Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

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Response regulation Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
Prostaglandin G/H synthase 2 (PTGS2)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Marker
Responsed Disease Formaldehyde-induced neurotoxicity [ICD-11: NE61]
Responsed Drug Formaldehyde Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

    Click to Show/Hide
Response regulation Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
Neutral amino acid transporter B(0) (SLC1A5)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Formaldehyde-induced neurotoxicity [ICD-11: NE61]
Responsed Drug Formaldehyde Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

    Click to Show/Hide
Response regulation Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
Glutaminase liver isoform, mitochondrial (GLS2)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Formaldehyde-induced neurotoxicity [ICD-11: NE61]
Responsed Drug Formaldehyde Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

    Click to Show/Hide
Response regulation Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
References
Ref 1 ATM orchestrates ferritinophagy and ferroptosis by phosphorylating NCOA4. Autophagy. 2023 Jul;19(7):2062-2077. doi: 10.1080/15548627.2023.2170960. Epub 2023 Feb 8.
Ref 2 Formaldehyde induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect. Toxicology. 2021 Jan 30;448:152650. doi: 10.1016/j.tox.2020.152650. Epub 2020 Nov 28.