Ferroptosis Regulator Information
General Information of the Ferroptosis Regulator (ID: REG10081)
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
HMGB1
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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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Hypoxic ischemic brain injury | ICD-11: 8B24 | |||
Responsed Drug | Glycyrrhizin | Phase 3 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
rPCNs (Rat primary cortical neurons) | ||||
In Vivo Model |
Male and female neonatal SpragueDawley rats on postpartum day 7 (P7) were provided by SPF Biotechnology (Beijing, China). Each animal was anesthetized with isoflurane (4% for induction, 2% for maintenance), the skin was incised, and the left common carotid artery was exposed. This artery was ligated with a 5-0 suture and cut, and the skin was sutured closed. Next, the pups recovered for 1 h with their mother. Subsequently, the pups were placed in a hypoxia chamber (8% O2 + 92% N2 mixture) for 2 h. After 2 h of hypoxia, the animals were placed back with their dam.
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Response regulation | Glycyrrhizin (GL) not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by hypoxic-ischemic brain damage (HIBD) in vivo. GL could suppress the occurrence of neuronal ferroptosis and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. | ||||
Experiment 2 Reporting the Ferroptosis Target of This Regulator | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute kidney failure | ICD-11: GB60 | |||
Responsed Drug | Isoliquiritigenin | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
HK-2 cells | Normal | Homo sapiens | CVCL_0302 | |
In Vivo Model |
Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently.
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Response regulation | Isoliquiritigenin (ISL) attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [3] | |||
Target for Ferroptosis | Marker/Suppressor | |||
Responsed Disease | Chronic kidney disease | ICD-11: GB61 | ||
Responsed Drug | D-Glucose | Investigative | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
NF-kappa B signaling pathway | hsa04064 | |||
Cell Process | Cell ferroptosis | |||
Cell proliferation | ||||
In Vitro Model |
SV40 MES 13 cells | Normal | Mus musculus | CVCL_5368 |
Response regulation | Erastin and high glucose both induced ferroptosis in mesangial cells. Suppression of HMGB1 restored cellular proliferation, prevented ROS and LDH generation, decreased ACSL4, PTGS2, and NOX1, and increased GPX4 levels in mesangial cells. Furthermore, nuclear factor E2-related factor 2 (Nrf2) was decreased in diabetic nephropathy (DN) patients and high glucose-mediated translocation of HMGB1 in mesangial cells. | |||
Unspecific Target [Unspecific Target]
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [4] | ||||
Responsed Disease | Sepsis | ICD-11: 1G40 | |||
Responsed Drug | Resveratrol | Phase 3 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Glutathione metabolism | hsa00480 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
hCMs (Human cardiomyocytes) | ||||
In Vivo Model |
Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1.
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Response regulation | Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice. | ||||
Experiment 2 Reporting the Ferroptosis Target of This Regulator | [5] | ||||
Responsed Disease | Cardiomyopathy | ICD-11: BC43 | |||
Responsed Drug | Dexrazoxane | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
Male Wistar rats (250-300 g,n = 230) were purchased from Vitalriver. Ten rats were recruited in each group in the experiment. The rats in the control, DOX, FER-1 + DOX, NEC-1 + DOX, 3-MA + DOX, and Emricasan + DOX groups were used for the overall survival analysis, and those from control and DOX groups were used for detection of the expression of PTGS2 in the indicated organs of rats.
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Response regulation | Dexrazoxane (DXZ) reduces cytotoxicity caused by Doxorubicin (DOX). HMGB1 was induced by DOX but was inhibited by DXZ or FER-1. Overexpression of HMGB1 promoted the ferroptosis and cardiotoxicity induced by DOX in the rats although silencing of HMGB1 showed opposite effects. | ||||
Experiment 3 Reporting the Ferroptosis Target of This Regulator | [6] | ||||
Responsed Disease | Hepatoblastoma | ICD-11: DB91 | |||
Responsed Drug | Glycyrrhizin | Phase 3 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | |
In Vivo Model |
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.
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Response regulation | The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. | ||||
Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [7] | ||||
Target for Ferroptosis | Marker/Suppressor/Driver | ||||
Responsed Disease | Myeloid leukaemia | ICD-11: 2B33 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
In Vitro Model |
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | ||
KG-1 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | ||
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
In Vivo Model |
Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection.
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Response regulation | HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice. | ||||
Prostaglandin G/H synthase 2 (PTGS2) [Driver; Marker]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [7] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Myeloid leukaemia | ICD-11: 2B33 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
In Vitro Model |
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | ||
KG-1 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | ||
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
In Vivo Model |
Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection.
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|
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Response regulation | HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice. | ||||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [Driver]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [8] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Pancreatic cancer | ICD-11: 2C10 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | |
MIA PaCa-2 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0428 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
Hep-G2 cells | Hepatoblastoma | Homo sapiens | CVCL_0027 | ||
In Vivo Model |
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and treated with IKE (imidazole ketone erastin; 40 mg/kg; i.p., once every other day) for 3 weeks, and then samples were collected and assayed.
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Response regulation | Pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4. | ||||
Hypoxic ischemic brain injury [ICD-11: 8B24]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Responsed Drug | Glycyrrhizin | Phase 3 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
rPCNs (Rat primary cortical neurons) | ||||
In Vivo Model |
Male and female neonatal SpragueDawley rats on postpartum day 7 (P7) were provided by SPF Biotechnology (Beijing, China). Each animal was anesthetized with isoflurane (4% for induction, 2% for maintenance), the skin was incised, and the left common carotid artery was exposed. This artery was ligated with a 5-0 suture and cut, and the skin was sutured closed. Next, the pups recovered for 1 h with their mother. Subsequently, the pups were placed in a hypoxia chamber (8% O2 + 92% N2 mixture) for 2 h. After 2 h of hypoxia, the animals were placed back with their dam.
Click to Show/Hide
|
||||
Response regulation | Glycyrrhizin (GL) not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by hypoxic-ischemic brain damage (HIBD) in vivo. GL could suppress the occurrence of neuronal ferroptosis and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. | ||||
Acute kidney failure [ICD-11: GB60]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [2] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Responsed Drug | Isoliquiritigenin | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
HK-2 cells | Normal | Homo sapiens | CVCL_0302 | |
In Vivo Model |
Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently.
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||||
Response regulation | Isoliquiritigenin (ISL) attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. | ||||
Chronic kidney disease [ICD-11: GB61]
In total 1 item(s) under this disease | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [3] | |||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | ||
Responsed Drug | D-Glucose | Investigative | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
NF-kappa B signaling pathway | hsa04064 | |||
Cell Process | Cell ferroptosis | |||
Cell proliferation | ||||
In Vitro Model |
SV40 MES 13 cells | Normal | Mus musculus | CVCL_5368 |
Response regulation | Erastin and high glucose both induced ferroptosis in mesangial cells. Suppression of HMGB1 restored cellular proliferation, prevented ROS and LDH generation, decreased ACSL4, PTGS2, and NOX1, and increased GPX4 levels in mesangial cells. Furthermore, nuclear factor E2-related factor 2 (Nrf2) was decreased in diabetic nephropathy (DN) patients and high glucose-mediated translocation of HMGB1 in mesangial cells. | |||
Sepsis [ICD-11: 1G40]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [4] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Responsed Drug | Resveratrol | Phase 3 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Glutathione metabolism | hsa00480 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
hCMs (Human cardiomyocytes) | ||||
In Vivo Model |
Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1.
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Response regulation | Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice. | ||||
Myeloid leukaemia [ICD-11: 2B33]
In total 2 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [7] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
In Vitro Model |
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | ||
KG-1 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | ||
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
In Vivo Model |
Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection.
Click to Show/Hide
|
||||
Response regulation | HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response | [7] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
In Vitro Model |
HL-60 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0002 | |
NB4 cells | Acute promyelocytic leukemia | Homo sapiens | CVCL_0005 | ||
KG-1 cells | Adult acute myeloid leukemia | Homo sapiens | CVCL_0374 | ||
U-937 cells | Adult acute monocytic leukemia | Homo sapiens | CVCL_0007 | ||
THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | ||
In Vivo Model |
Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection.
Click to Show/Hide
|
||||
Response regulation | HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice. | ||||
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [8] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | |
MIA PaCa-2 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0428 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
Hep-G2 cells | Hepatoblastoma | Homo sapiens | CVCL_0027 | ||
In Vivo Model |
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and treated with IKE (imidazole ketone erastin; 40 mg/kg; i.p., once every other day) for 3 weeks, and then samples were collected and assayed.
Click to Show/Hide
|
||||
Response regulation | Pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4. | ||||
Cardiomyopathy [ICD-11: BC43]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [5] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Responsed Drug | Dexrazoxane | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
Male Wistar rats (250-300 g,n = 230) were purchased from Vitalriver. Ten rats were recruited in each group in the experiment. The rats in the control, DOX, FER-1 + DOX, NEC-1 + DOX, 3-MA + DOX, and Emricasan + DOX groups were used for the overall survival analysis, and those from control and DOX groups were used for detection of the expression of PTGS2 in the indicated organs of rats.
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|
||||
Response regulation | Dexrazoxane (DXZ) reduces cytotoxicity caused by Doxorubicin (DOX). HMGB1 was induced by DOX but was inhibited by DXZ or FER-1. Overexpression of HMGB1 promoted the ferroptosis and cardiotoxicity induced by DOX in the rats although silencing of HMGB1 showed opposite effects. | ||||
Hepatoblastoma [ICD-11: DB91]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [6] | ||||
Target Regulator | High mobility group protein B1 (HMGB1) | Protein coding | |||
Responsed Drug | Glycyrrhizin | Phase 3 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | |
In Vivo Model |
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.
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Response regulation | The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. | ||||
Glycyrrhizin
[Phase 3]
In total 2 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Suppressor | ||||
Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | |||
Responsed Disease | Hypoxic ischemic brain injury | ICD-11: 8B24 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
rPCNs (Rat primary cortical neurons) | ||||
In Vivo Model |
Male and female neonatal SpragueDawley rats on postpartum day 7 (P7) were provided by SPF Biotechnology (Beijing, China). Each animal was anesthetized with isoflurane (4% for induction, 2% for maintenance), the skin was incised, and the left common carotid artery was exposed. This artery was ligated with a 5-0 suture and cut, and the skin was sutured closed. Next, the pups recovered for 1 h with their mother. Subsequently, the pups were placed in a hypoxia chamber (8% O2 + 92% N2 mixture) for 2 h. After 2 h of hypoxia, the animals were placed back with their dam.
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Response regulation | Glycyrrhizin (GL) not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by hypoxic-ischemic brain damage (HIBD) in vivo. GL could suppress the occurrence of neuronal ferroptosis and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. | ||||
Experiment 2 Reporting the Ferroptosis-centered Drug Response | [6] | ||||
Drug for Ferroptosis | Suppressor | ||||
Response Target | Unspecific Target | ||||
Responsed Disease | Hepatoblastoma | ICD-11: DB91 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | |
In Vivo Model |
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.
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Response regulation | The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. | ||||
Isoliquiritigenin
[Investigative]
In total 1 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [2] | ||||
Drug for Ferroptosis | Suppressor | ||||
Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | |||
Responsed Disease | Acute kidney failure | ICD-11: GB60 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
HK-2 cells | Normal | Homo sapiens | CVCL_0302 | |
In Vivo Model |
Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently.
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Response regulation | Isoliquiritigenin (ISL) attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. | ||||
D-Glucose
[Investigative]
In total 1 item(s) under this drug | ||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [3] | |||
Drug for Ferroptosis | Inducer | |||
Response Target | Nuclear factor erythroid 2-related factor 2 (NFE2L2) | Suppressor; Marker | ||
Responsed Disease | Chronic kidney disease | ICD-11: GB61 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
NF-kappa B signaling pathway | hsa04064 | |||
Cell Process | Cell ferroptosis | |||
Cell proliferation | ||||
In Vitro Model |
SV40 MES 13 cells | Normal | Mus musculus | CVCL_5368 |
Response regulation | Erastin and high glucose both induced ferroptosis in mesangial cells. Suppression of HMGB1 restored cellular proliferation, prevented ROS and LDH generation, decreased ACSL4, PTGS2, and NOX1, and increased GPX4 levels in mesangial cells. Furthermore, nuclear factor E2-related factor 2 (Nrf2) was decreased in diabetic nephropathy (DN) patients and high glucose-mediated translocation of HMGB1 in mesangial cells. | |||
Resveratrol
[Phase 3]
In total 1 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [4] | ||||
Drug for Ferroptosis | Suppressor | ||||
Response Target | Unspecific Target | ||||
Responsed Disease | Sepsis | ICD-11: 1G40 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Glutathione metabolism | hsa00480 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
hCMs (Human cardiomyocytes) | ||||
In Vivo Model |
Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1.
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Response regulation | Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice. | ||||
Dexrazoxane
[Investigative]
In total 1 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [5] | ||||
Drug for Ferroptosis | Suppressor | ||||
Response Target | Unspecific Target | ||||
Responsed Disease | Cardiomyopathy | ICD-11: BC43 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
Male Wistar rats (250-300 g,n = 230) were purchased from Vitalriver. Ten rats were recruited in each group in the experiment. The rats in the control, DOX, FER-1 + DOX, NEC-1 + DOX, 3-MA + DOX, and Emricasan + DOX groups were used for the overall survival analysis, and those from control and DOX groups were used for detection of the expression of PTGS2 in the indicated organs of rats.
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Response regulation | Dexrazoxane (DXZ) reduces cytotoxicity caused by Doxorubicin (DOX). HMGB1 was induced by DOX but was inhibited by DXZ or FER-1. Overexpression of HMGB1 promoted the ferroptosis and cardiotoxicity induced by DOX in the rats although silencing of HMGB1 showed opposite effects. | ||||
References