Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10475)
Regulator Name DNA damage-inducible transcript 3 protein (DDIT3)
Synonyms
CHOP; CHOP10; GADD153; C/EBP zeta; C/EBP-homologous protein; C/EBP-homologous protein 10; CCAAT/enhancer-binding protein homologous protein; Growth arrest and DNA damage-inducible protein GADD153
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Gene Name DDIT3
Gene ID 1649
Regulator Type Protein coding
Uniprot ID P35638
Sequence
MAAESLPFSFGTLSSWELEAWYEDLQEVLSSDENGGTYVSPPGNEEEESKIFTTLDPASL
AWLTEEEPEPAEVTSTSQSPHSPDSSQSSLAQEEEEEDQGRTRKRKQSGHSPARAGKQRM
KEKEQENERKVAQLAEENERLKQEIERLTREVEATRRALIDRMVNLHQA

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Family BZIP family
Function
Multifunctional transcription factor in endoplasmic reticulum (ER) stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes (By similarity). Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes (By similarity). Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L. Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG). Together with ATF4, mediates ER- mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity. Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response (By similarity). Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling (By similarity).

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HGNC ID
HGNC:2726
KEGG ID hsa:1649
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
DDIT3 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Traumatic brain injury ICD-11: NA07
 Disease Info 
Responsed Drug Baicalein Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

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Response regulation Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
Traumatic brain injury [ICD-11: NA07]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator DNA damage-inducible transcript 3 protein (DDIT3) Protein coding
 Regulator Info 
Responsed Drug Baicalein Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

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Response regulation Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
Baicalein [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Unspecific Target
Responsed Disease Traumatic brain injury ICD-11: NA07
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 rRHs (Rat right hemispheres)
In Vivo Model
Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg).

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Response regulation Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC.
References
Ref 1 BAICALEIN RELIEVES BRAIN INJURY VIA INHIBITING FERROPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN A RAT MODEL OF CARDIAC ARREST. Shock. 2023 Mar 1;59(3):434-441. doi: 10.1097/SHK.0000000000002058. Epub 2022 Nov 26.