Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10510)
Regulator Name Glutathione reductase, mitochondrial (GSR)
Synonyms
GLUR; GRD1;
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Gene Name GSR
Gene ID 2936
Regulator Type Protein coding
Uniprot ID P00390
Sequence
MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAMACRQEPQPQGPPPAAG
AVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTCVNVGCVPKKVMWNTAVHS
EFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQNNLTKSHIEIIRGHAAFTSDP
KPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLGITSDGFFQLEELPGRSVIVGAG
YIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMISTNCTEELENAGVEVLKFSQVKEVKK
TLSGLEVSMVTAVPGRLPVMTMIPDVDCLLWAIGRVPNTKDLSLNKLGIQTDDKGHIIVD
EFQNTNVKGIYAVGDVCGKALLTPVAIAAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPP
IGTVGLTEDEAIHKYGIENVKTYSTSFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQ
GLGCDEMLQGFAVAVKMGATKADFDNTVAIHPTSSEELVTLR

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Family Class-I pyridine nucleotide-disulfide oxidoreductase family
Function
Maintains high levels of reduced glutathione in the cytosol.

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HGNC ID
HGNC:4623
KEGG ID hsa:2936
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
GSR 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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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Drug Carmustine Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In Vivo Model
Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation.

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Response regulation The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutathione reductase, mitochondrial (GSR) Protein coding
 Regulator Info 
Responsed Drug Carmustine Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In Vivo Model
Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation.

    Click to Show/Hide
Response regulation The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance.
Carmustine [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In Vivo Model
Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation.

    Click to Show/Hide
Response regulation The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance.
References
Ref 1 SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase. Cell Death Dis. 2023 Jan 12;14(1):22. doi: 10.1038/s41419-023-05558-w.