Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10131)
Regulator Name Peroxiredoxin-6 (PRDX6)
Synonyms
AOP2, KIAA0106; 1-Cys peroxiredoxin; 24 kDa protein; Acidic calcium-independent phospholipase A2; Antioxidant protein 2; Glutathione-dependent peroxiredoxin; Non-selenium glutathione peroxidase; Red blood cells page spot 12
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Gene Name PRDX6
Gene ID 9588
Regulator Type Protein coding
Uniprot ID P30041
Sequence
MPGGLLLGDVAPNFEANTTVGRIRFHDFLGDSWGILFSHPRDFTPVCTTELGRAAKLAPE
FAKRNVKLIALSIDSVEDHLAWSKDINAYNCEEPTEKLPFPIIDDRNRELAILLGMLDPA
EKDEKGMPVTARVVFVFGPDKKLKLSILYPATTGRNFDEILRVVISLQLTAEKRVATPVD
WKDGDSVMVLPTIPEEEAKKLFPKGVFTKELPSGKKYLRYTPQP

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Family Peroxiredoxin family
Function
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH. Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis. Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3- phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero- 3-phosphocholine or PC). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate.

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HGNC ID
HGNC:16753
KEGG ID hsa:9588
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PRDX6 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 Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HL-1 cells Normal Mus musculus CVCL_0303
hBMSCs (Bone marrow stromal cells)
In Vivo Model
A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery.

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Response regulation Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/ PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells.
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 [1]
Target for Ferroptosis Driver
Responsed Disease Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HL-1 cells Normal Mus musculus CVCL_0303
hBMSCs (Bone marrow stromal cells)
In Vivo Model
A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery.

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Response regulation Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/ PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells.
Cystine/glutamate transporter (SLC7A11) [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 Suppressor
Responsed Disease Chronic kidney disease ICD-11: GB61
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MPC-5 cells Normal Mus musculus CVCL_AS87
In Vivo Model
Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established.

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Response regulation Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice.
Ischemia/reperfusion injury [ICD-11: DB98]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Peroxiredoxin-6 (PRDX6) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HL-1 cells Normal Mus musculus CVCL_0303
hBMSCs (Bone marrow stromal cells)
In Vivo Model
A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery.

    Click to Show/Hide
Response regulation Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/ PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Peroxiredoxin-6 (PRDX6) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HL-1 cells Normal Mus musculus CVCL_0303
hBMSCs (Bone marrow stromal cells)
In Vivo Model
A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery.

    Click to Show/Hide
Response regulation Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/ PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells.
Chronic kidney disease [ICD-11: GB61]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Peroxiredoxin-6 (PRDX6) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MPC-5 cells Normal Mus musculus CVCL_AS87
In Vivo Model
Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established.

    Click to Show/Hide
Response regulation Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice.
References
Ref 1 The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis. Nutr Metab Cardiovasc Dis. 2022 Feb;32(2):515-527. doi: 10.1016/j.numecd.2021.10.017. Epub 2021 Nov 3.
Ref 2 Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis. Life Sci. 2021 Aug 1;278:119529. doi: 10.1016/j.lfs.2021.119529. Epub 2021 Apr 21.