Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10468)
Regulator Name Aldo-keto reductase family 1 member C2 (AKR1C2)
Synonyms
DDH2; 3-alpha-HSD3; Chlordecone reductase homolog HAKRD; Dihydrodiol dehydrogenase 2; Dihydrodiol dehydrogenase/bile acid-binding protein; Type III 3-alpha-hydroxysteroid dehydrogenase
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Gene Name AKR1C2
Gene ID 1646
Regulator Type Protein coding
Uniprot ID P52895
Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV
SVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKP
GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN
RNVRYLTLDIFAGPPNYPFSDEY

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Family Aldo/keto reductase family
Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH. Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens. Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3- alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha- androstane-3-alpha,17-beta-diol (3-alpha-diol). Also specifically able to produce 17beta-hydroxy-5alpha-androstan-3-one/5alphaDHT. May also reduce conjugated steroids such as 5alpha- dihydrotestosterone sulfate. Displays affinity for bile acids.

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HGNC ID
HGNC:385
KEGG ID hsa:1646
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
AKR1C2 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Essential hypertension ICD-11: BA00
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
Aortic smooth muscle cells were isolated from wild-type male 6-8-week and CSE-knockout mice. Mice were sacrificed by decapitation, followed by separating the aorta via removing the fatty tissue and vascular adventitia. Then, the mouse aorta was cut into pieces and allowed for digestion for 8 h in the DMEM containing collagenase type 1. The obtained VSMCs were centrifuged at 300 xg for 5 min, and the pellet was resuspended in the DMEM supplemented with 10% FBS, 2 mM l-glutamine, and 100 U/mL penicillin/streptomycin. The medium was replaced every 2 days.

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Response regulation Aortic GPX4 (a core regulator of ferroptosis) significantly downregulated association with VSMC novel phenotype elevation in SHR rats and hypertension patients. The ferroptosis inhibitor ferrostatin-1 (Fer-1) administration blocked HHP-induced VSMC inflammatory (CXCL2 expression) and endothelial function inhibitory ( AKR1C2 expression) phenotyping switch association with elevation in the GPX4 expression, reduction in the reactive oxygen species (ROS), and lipid peroxidation production.
Essential hypertension [ICD-11: BA00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Aldo-keto reductase family 1 member C2 (AKR1C2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
Aortic smooth muscle cells were isolated from wild-type male 6-8-week and CSE-knockout mice. Mice were sacrificed by decapitation, followed by separating the aorta via removing the fatty tissue and vascular adventitia. Then, the mouse aorta was cut into pieces and allowed for digestion for 8 h in the DMEM containing collagenase type 1. The obtained VSMCs were centrifuged at 300 xg for 5 min, and the pellet was resuspended in the DMEM supplemented with 10% FBS, 2 mM l-glutamine, and 100 U/mL penicillin/streptomycin. The medium was replaced every 2 days.

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Response regulation Aortic GPX4 (a core regulator of ferroptosis) significantly downregulated association with VSMC novel phenotype elevation in SHR rats and hypertension patients. The ferroptosis inhibitor ferrostatin-1 (Fer-1) administration blocked HHP-induced VSMC inflammatory (CXCL2 expression) and endothelial function inhibitory ( AKR1C2 expression) phenotyping switch association with elevation in the GPX4 expression, reduction in the reactive oxygen species (ROS), and lipid peroxidation production.
References
Ref 1 Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 2014 May 20;3:e02523. doi: 10.7554/eLife.02523.