General Information of the Ferroptosis Regulator (ID: REG10031)
Regulator Name Maleylacetoacetate isomerase (GSTZ1)
Synonyms
MAAI; GSTZ1-1; Glutathione S-transferase zeta 1
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Gene Name GSTZ1
Gene ID 2954
Regulator Type Protein coding
Uniprot ID O43708
Sequence
MQAGKPILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKDRGQQFSKDFQALNPMKQVP
TLKIDGITIHQSLAIIEYLEEMRPTPRLLPQDPKKRASVRMISDLIAGGIQPLQNLSVLK
QVGEEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCLVPQVANAERFKVDL
TPYPTISSINKRLLVLEAFQVSHPCRQPDTPTELRA

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Family Zeta family
Function
Bifunctional enzyme showing minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1,3- diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with T-butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid.

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HGNC ID
HGNC:4643
KEGG ID hsa:2954
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
GSTZ1 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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Browse Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 1 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
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice were divided into five groups as follows: WT + DMSO (control), WT + Sora, Gstz1-/-+DMSO, Gstz1-/-+Sora, and Gstz1-/-+Sora + RSL3. Each group included three male and three female mice. At 2 weeks of age, all mice were administered an intraperitoneal injection of diethylnitrosamine (DEN; Sigma, St. Louis, MO, USA) at a dose of 75 mg/kg. At the third week, the mice were intraperitoneally administered carbon tetrachloride (CCl4; Macklin, Shanghai, China) at 2 ml/kg twice a week for 12 weeks. In the WT + Sora and Gstz1-/-+Sora group, the mice at 22 weeks were administered intraperitoneally sorafenib (30 mg/kg) every 2 days for 4 weeks until euthanasia. In the Gstz1-/-+Sora + RSL3 group, in addition to sorafenib administration as described above, the mice were injected intraperitoneally with RSL3 (10 mg/kg) every 2 days for 4 weeks at the same weeks.

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Response regulation GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in hepatocellular carcinoma (HCC) cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
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 [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice were divided into five groups as follows: WT + DMSO (control), WT + Sora, Gstz1-/-+DMSO, Gstz1-/-+Sora, and Gstz1-/-+Sora + RSL3. Each group included three male and three female mice. At 2 weeks of age, all mice were administered an intraperitoneal injection of diethylnitrosamine (DEN; Sigma, St. Louis, MO, USA) at a dose of 75 mg/kg. At the third week, the mice were intraperitoneally administered carbon tetrachloride (CCl4; Macklin, Shanghai, China) at 2 ml/kg twice a week for 12 weeks. In the WT + Sora and Gstz1-/-+Sora group, the mice at 22 weeks were administered intraperitoneally sorafenib (30 mg/kg) every 2 days for 4 weeks until euthanasia. In the Gstz1-/-+Sora + RSL3 group, in addition to sorafenib administration as described above, the mice were injected intraperitoneally with RSL3 (10 mg/kg) every 2 days for 4 weeks at the same weeks.

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Response regulation GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in hepatocellular carcinoma (HCC) cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
Hepatocellular carcinoma [ICD-11: 2C12]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Maleylacetoacetate isomerase (GSTZ1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice were divided into five groups as follows: WT + DMSO (control), WT + Sora, Gstz1-/-+DMSO, Gstz1-/-+Sora, and Gstz1-/-+Sora + RSL3. Each group included three male and three female mice. At 2 weeks of age, all mice were administered an intraperitoneal injection of diethylnitrosamine (DEN; Sigma, St. Louis, MO, USA) at a dose of 75 mg/kg. At the third week, the mice were intraperitoneally administered carbon tetrachloride (CCl4; Macklin, Shanghai, China) at 2 ml/kg twice a week for 12 weeks. In the WT + Sora and Gstz1-/-+Sora group, the mice at 22 weeks were administered intraperitoneally sorafenib (30 mg/kg) every 2 days for 4 weeks until euthanasia. In the Gstz1-/-+Sora + RSL3 group, in addition to sorafenib administration as described above, the mice were injected intraperitoneally with RSL3 (10 mg/kg) every 2 days for 4 weeks at the same weeks.

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Response regulation GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in hepatocellular carcinoma (HCC) cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Maleylacetoacetate isomerase (GSTZ1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SNU-449 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0454
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice were divided into five groups as follows: WT + DMSO (control), WT + Sora, Gstz1-/-+DMSO, Gstz1-/-+Sora, and Gstz1-/-+Sora + RSL3. Each group included three male and three female mice. At 2 weeks of age, all mice were administered an intraperitoneal injection of diethylnitrosamine (DEN; Sigma, St. Louis, MO, USA) at a dose of 75 mg/kg. At the third week, the mice were intraperitoneally administered carbon tetrachloride (CCl4; Macklin, Shanghai, China) at 2 ml/kg twice a week for 12 weeks. In the WT + Sora and Gstz1-/-+Sora group, the mice at 22 weeks were administered intraperitoneally sorafenib (30 mg/kg) every 2 days for 4 weeks until euthanasia. In the Gstz1-/-+Sora + RSL3 group, in addition to sorafenib administration as described above, the mice were injected intraperitoneally with RSL3 (10 mg/kg) every 2 days for 4 weeks at the same weeks.

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Response regulation GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in hepatocellular carcinoma (HCC) cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.
References
Ref 1 GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis. Cell Death Dis. 2021 Apr 30;12(5):426. doi: 10.1038/s41419-021-03718-4.