Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10203)
Regulator Name Peroxisome proliferator-activated receptor alpha (PPARA)
Synonyms
NR1C1, PPAR; Nuclear receptor subfamily 1 group C member 1
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Gene Name PPARA
Gene ID 5465
Regulator Type Protein coding
Uniprot ID Q07869
Sequence
MVDTESPLCPLSPLEAGDLESPLSEEFLQEMGNIQEISQSIGEDSSGSFGFTEYQYLGSC
PGSDGSVITDTLSPASSPSSVTYPVVPGSVDESPSGALNIECRICGDKASGYHYGVHACE
GCKGFFRRTIRLKLVYDKCDRSCKIQKKNRNKCQYCRFHKCLSVGMSHNAIRFGRMPRSE
KAKLKAEILTCEHDIEDSETADLKSLAKRIYEAYLKNFNMNKVKARVILSGKASNNPPFV
IHDMETLCMAEKTLVAKLVANGIQNKEAEVRIFHCCQCTSVETVTELTEFAKAIPGFANL
DLNDQVTLLKYGVYEAIFAMLSSVMNKDGMLVAYGNGFITREFLKSLRKPFCDIMEPKFD
FAMKFNALELDDSDISLFVAAIICCGDRPGLLNVGHIEKMQEGIVHVLRLHLQSNHPDDI
FLFPKLLQKMADLRQLVTEHAQLVQIIKKTESDAALHPLLQEIYRDMY

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Family Nuclear hormone receptor family
Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn- glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.

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HGNC ID
HGNC:9232
KEGG ID hsa:5465
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PPARA 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
Serotransferrin (TF) [Driver; Suppressor; 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/Suppressor/Driver
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Hepa 1-6 cells Hepatocellular carcinoma Mus musculus CVCL_0327
In Vivo Model
C57BL/6J SPF mice were purchased from Huazhong Agricultural University Experimental Animal Center. Mice were given tertian intraperitoneal injections of either PBS (control) or dextriferron (500 mg/kg body weight) for 2 weeks and then sacrificed. Mice were given a daily intraperitoneal injection of either vehicle or ferrostatin-1 (Fer1, 1 mg/kg body weight) for 3 weeks before sacrificed.

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Response regulation PPARa activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF (TF), suggesting that PPAR may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries in Hepatocellular carcinomaHepatocellular carcinoma.
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Hepa 1-6 cells Hepatocellular carcinoma Mus musculus CVCL_0327
In Vivo Model
C57BL/6J SPF mice were purchased from Huazhong Agricultural University Experimental Animal Center. Mice were given tertian intraperitoneal injections of either PBS (control) or dextriferron (500 mg/kg body weight) for 2 weeks and then sacrificed. Mice were given a daily intraperitoneal injection of either vehicle or ferrostatin-1 (Fer1, 1 mg/kg body weight) for 3 weeks before sacrificed.

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Response regulation PPARa activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF, suggesting that PPAR may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries in Hepatocellular carcinoma.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Immunoglobulin A nephropathy ICD-11: MF8Y
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hMCs (Human mesangial cells)
Response regulation In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis.
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [Driver]
 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 Immunoglobulin A nephropathy ICD-11: MF8Y
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hMCs (Human mesangial cells)
Response regulation In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Peroxisome proliferator-activated receptor alpha (PPARA) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Hepa 1-6 cells Hepatocellular carcinoma Mus musculus CVCL_0327
In Vivo Model
C57BL/6J SPF mice were purchased from Huazhong Agricultural University Experimental Animal Center. Mice were given tertian intraperitoneal injections of either PBS (control) or dextriferron (500 mg/kg body weight) for 2 weeks and then sacrificed. Mice were given a daily intraperitoneal injection of either vehicle or ferrostatin-1 (Fer1, 1 mg/kg body weight) for 3 weeks before sacrificed.

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Response regulation PPARa activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF (TF), suggesting that PPAR may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries in Hepatocellular carcinomaHepatocellular carcinoma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Peroxisome proliferator-activated receptor alpha (PPARA) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Hepa 1-6 cells Hepatocellular carcinoma Mus musculus CVCL_0327
In Vivo Model
C57BL/6J SPF mice were purchased from Huazhong Agricultural University Experimental Animal Center. Mice were given tertian intraperitoneal injections of either PBS (control) or dextriferron (500 mg/kg body weight) for 2 weeks and then sacrificed. Mice were given a daily intraperitoneal injection of either vehicle or ferrostatin-1 (Fer1, 1 mg/kg body weight) for 3 weeks before sacrificed.

    Click to Show/Hide
Response regulation PPARa activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF, suggesting that PPAR may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries in Hepatocellular carcinoma.
Immunoglobulin A nephropathy [ICD-11: MF8Y]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Peroxisome proliferator-activated receptor alpha (PPARA) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hMCs (Human mesangial cells)
Response regulation In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Peroxisome proliferator-activated receptor alpha (PPARA) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hMCs (Human mesangial cells)
Response regulation In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis.
References
Ref 1 PPAR alleviates iron overload-induced ferroptosis in mouse liver. EMBO Rep. 2022 Aug 3;23(8):e52280. doi: 10.15252/embr.202052280. Epub 2022 Jun 15.
Ref 2 Downregulation of PPAR mediates FABP1 expression, contributing to IgA nephropathy by stimulating ferroptosis in human mesangial cells. Int J Biol Sci. 2022 Aug 29;18(14):5438-5458. doi: 10.7150/ijbs.74675. eCollection 2022.