Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10232)
Regulator Name Hypoxia-inducible factor 1-alpha (HIF1A)
Synonyms
ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; PAS domain-containing protein 8
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Gene Name HIF1A
Gene ID 3091
Regulator Type Protein coding
Uniprot ID Q16665
Sequence
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN

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Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.

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HGNC ID
HGNC:4910
KEGG ID hsa:3091
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
HIF1A 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).
Browse Target
Browse Disease
Browse Drug
Prostaglandin G/H synthase 2 (PTGS2) [Driver; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Responsed Drug Atorvastatin Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mMTs (Mouse myocardial tissues)
In Vivo Model
Rats were anesthetized intraperitoneally with 3% pentobarbital sodium (40 mg/kg). After mechanical ventilation, the rats were subjected to a thoracotomy to expose the hearts and ascending aorta. Finally, the ascending aorta was occluded for 10 s, and 8,000 polyester microspheres (diameter 42 um, Biosphere Medical, Rockland, MA, United States ) were injected into the left ventricle at the same time, while the sham-operated rats received the same dosage of normal saline instead. Forin vivotreatment, rats were treated with recombinant adeno-associated virus 9 (rAAV9)-GFP-shPtsg2 (Hanbio, Shanghai, China) or rAAV9-GFP-shHif1a (Genechem, Shanghai, China) at a dose of 1 x 1012 VG in 200 uL salineviaa single tail vein before CME. Deferoxamine (DFO) was purchased from Selleck (Shanghai, China) and administered intraperitoneally at a dose of 100 mg/kg for 7 days before CME. ATV (Pfizer, New York, United Kingdom) was administered intragastrically at a dose of 10 mg/kg for 7 days before CME.

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Response regulation Ptgs2 was positively regulated by Hif1a and contributed to ferroptosis-dependent myocardial injury and inflammation. Furthermore, Atorvastatin protects against ferroptosis and inflammation induced by CME via the Hif1a/Ptgs2 pathway.
Heme oxygenase 1 (HMOX1) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Driver
Responsed Disease Testicular injury ICD-11: NB9Z
 Disease Info 
Responsed Drug Diethylhexylphthalate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
HIF-1 signaling pathway hsa04066
Cell Process Cell ferroptosis
In Vitro Model
 TM3 cells Normal Mus musculus CVCL_4326
TM4 cells Normal Mus musculus CVCL_4327
In Vivo Model
Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).

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Response regulation Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway.
Acute myocardial infarction [ICD-11: BA41]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Hypoxia-inducible factor 1-alpha (HIF1A) Protein coding
 Regulator Info 
Responsed Drug Atorvastatin Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mMTs (Mouse myocardial tissues)
In Vivo Model
Rats were anesthetized intraperitoneally with 3% pentobarbital sodium (40 mg/kg). After mechanical ventilation, the rats were subjected to a thoracotomy to expose the hearts and ascending aorta. Finally, the ascending aorta was occluded for 10 s, and 8,000 polyester microspheres (diameter 42 um, Biosphere Medical, Rockland, MA, United States ) were injected into the left ventricle at the same time, while the sham-operated rats received the same dosage of normal saline instead. Forin vivotreatment, rats were treated with recombinant adeno-associated virus 9 (rAAV9)-GFP-shPtsg2 (Hanbio, Shanghai, China) or rAAV9-GFP-shHif1a (Genechem, Shanghai, China) at a dose of 1 x 1012 VG in 200 uL salineviaa single tail vein before CME. Deferoxamine (DFO) was purchased from Selleck (Shanghai, China) and administered intraperitoneally at a dose of 100 mg/kg for 7 days before CME. ATV (Pfizer, New York, United Kingdom) was administered intragastrically at a dose of 10 mg/kg for 7 days before CME.

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Response regulation Ptgs2 was positively regulated by Hif1a and contributed to ferroptosis-dependent myocardial injury and inflammation. Furthermore, Atorvastatin protects against ferroptosis and inflammation induced by CME via the Hif1a/Ptgs2 pathway.
Testicular injury [ICD-11: NB9Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Hypoxia-inducible factor 1-alpha (HIF1A) Protein coding
 Regulator Info 
Responsed Drug Diethylhexylphthalate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
HIF-1 signaling pathway hsa04066
Cell Process Cell ferroptosis
In Vitro Model
 TM3 cells Normal Mus musculus CVCL_4326
TM4 cells Normal Mus musculus CVCL_4327
In Vivo Model
Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).

    Click to Show/Hide
Response regulation Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway.
Atorvastatin [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 Prostaglandin G/H synthase 2 (PTGS2) Driver; Marker
 Target Info 
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mMTs (Mouse myocardial tissues)
In Vivo Model
Rats were anesthetized intraperitoneally with 3% pentobarbital sodium (40 mg/kg). After mechanical ventilation, the rats were subjected to a thoracotomy to expose the hearts and ascending aorta. Finally, the ascending aorta was occluded for 10 s, and 8,000 polyester microspheres (diameter 42 um, Biosphere Medical, Rockland, MA, United States ) were injected into the left ventricle at the same time, while the sham-operated rats received the same dosage of normal saline instead. Forin vivotreatment, rats were treated with recombinant adeno-associated virus 9 (rAAV9)-GFP-shPtsg2 (Hanbio, Shanghai, China) or rAAV9-GFP-shHif1a (Genechem, Shanghai, China) at a dose of 1 x 1012 VG in 200 uL salineviaa single tail vein before CME. Deferoxamine (DFO) was purchased from Selleck (Shanghai, China) and administered intraperitoneally at a dose of 100 mg/kg for 7 days before CME. ATV (Pfizer, New York, United Kingdom) was administered intragastrically at a dose of 10 mg/kg for 7 days before CME.

    Click to Show/Hide
Response regulation Ptgs2 was positively regulated by Hif1a and contributed to ferroptosis-dependent myocardial injury and inflammation. Furthermore, Atorvastatin protects against ferroptosis and inflammation induced by CME via the Hif1a/Ptgs2 pathway.
Diethylhexylphthalate [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [2]
Drug for Ferroptosis Inducer
Response Target Heme oxygenase 1 (HMOX1) Driver; Suppressor
 Target Info 
Responsed Disease Testicular injury ICD-11: NB9Z
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
HIF-1 signaling pathway hsa04066
Cell Process Cell ferroptosis
In Vitro Model
 TM3 cells Normal Mus musculus CVCL_4326
TM4 cells Normal Mus musculus CVCL_4327
In Vivo Model
Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).

    Click to Show/Hide
Response regulation Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway.
References
Ref 1 Atorvastatin attenuates ferroptosis-dependent myocardial injury and inflammation following coronary microembolization via the Hif1a/Ptgs2 pathway. Front Pharmacol. 2022 Dec 8;13:1057583. doi: 10.3389/fphar.2022.1057583. eCollection 2022.
Ref 2 Di-(2-ethylhexyl) phthalate exposure leads to ferroptosis via the HIF-1/HO-1 signaling pathway in mouse testes. J Hazard Mater. 2022 Mar 15;426:127807. doi: 10.1016/j.jhazmat.2021.127807. Epub 2021 Nov 24.