Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10065)
Target Name Glutamate--cysteine ligase regulatory subunit (GCLM)
Synonyms
GLCLR; GCS light chain; Gamma-ECS regulatory subunit; Gamma-glutamylcysteine synthetase regulatory subunit; Glutamate--cysteine ligase modifier subunit
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Gene Name GCLM
Sequence
MGTDSRAAKALLARARTLHLQTGNLLNWGRLRKKCPSTHSEELHDCIQKTLNEWSSQINP
DLVREFPDVLECTVSHAVEKINPDEREEMKVSAKLFIVESNSSSSTRSAVDMACSVLGVA
QLDSVIIASPPIEDGVNLSLEHLQPYWEELENLVQSKKIVAIGTSDLDKTQLEQLYQWAQ
VKPNSNQVNLASCCVMPPDLTAFAKQFDIQLLTHNDPKELLSEASFQEALQESIPDIQAH
EWVPLWLLRYSVIVKSRGIIKSKGYILQAKRRGS

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Family Aldo/keto reductase family
Function
Sulfur metabolism; glutathione biosynthesis; glutathione from L-cysteine and L-glutamate: step 1/2.

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Gene ID 2730
Uniprot ID
P48507
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
GCLM can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
Mitogen-activated protein kinase 8 (MAPK8)
 Regulator Info 
Cerebral ischemia [ICD-11: 8B10]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Driver
Responsed Drug L-F001 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
Response Description L-F001 could restore GPX4 and glutamate-cysteine ligase modifier subunit (GCLM) levels, and significantly deceased Cyclooxygenase (COX-2) levels to rescue the lipid peroxidation imbalance. And L-F001 could reduce RSL3-induced c-Jun N-terminal kinase (JNK) activation, which might be a potential drug target for for the therapy of ferroptosis-related diseases, such as cerebral ischemia.
hsa-miR-145-5p (miRNA)
 Regulator Info 
Prolactinoma [ICD-11: 2F37]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Drug Cabergoline Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MMQ cells Pituitary gland neoplasm Rattus norvegicus CVCL_2117
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed.

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Response Description GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients.
CircOMA1 (circRNA)
 Regulator Info 
Prolactinoma [ICD-11: 2F37]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Responsed Drug Cabergoline Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MMQ cells Pituitary gland neoplasm Rattus norvegicus CVCL_2117
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed.

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Response Description GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients.
Unspecific Regulator
Gastric cancer [ICD-11: 2B72]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Responsed Drug Andrographis Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 MKN74 cells Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
Response Description Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM.
Mitogen-activated protein kinase 8 (MAPK8)
 Regulator Info 
L-F001 [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Driver
Responsed Disease Cerebral ischemia [ICD-11: 8B10]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
Response Description L-F001 could restore GPX4 and glutamate-cysteine ligase modifier subunit (GCLM) levels, and significantly deceased Cyclooxygenase (COX-2) levels to rescue the lipid peroxidation imbalance. And L-F001 could reduce RSL3-induced c-Jun N-terminal kinase (JNK) activation, which might be a potential drug target for for the therapy of ferroptosis-related diseases, such as cerebral ischemia.
hsa-miR-145-5p (miRNA)
 Regulator Info 
Cabergoline [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Disease Prolactinoma [ICD-11: 2F37]
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MMQ cells Pituitary gland neoplasm Rattus norvegicus CVCL_2117
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed.

    Click to Show/Hide
Response Description GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients.
CircOMA1 (circRNA)
 Regulator Info 
Cabergoline [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Responsed Disease Prolactinoma [ICD-11: 2F37]
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MMQ cells Pituitary gland neoplasm Rattus norvegicus CVCL_2117
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed.

    Click to Show/Hide
Response Description GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients.
Unspecific Regulator
Andrographis [Approved]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Responsed Disease Gastric cancer [ICD-11: 2B72]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model MKN74 cells Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
NUGC-4 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_3082
Response Description Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM.
References
Ref 1 L-F001, a Multifunctional Fasudil-Lipoic Acid Dimer Prevents RSL3-Induced Ferroptosis via Maintaining Iron Homeostasis and Inhibiting JNK in HT22 Cells. Front Cell Neurosci. 2022 Mar 31;16:774297. doi: 10.3389/fncel.2022.774297. eCollection 2022.
Ref 2 CircOMA1 modulates cabergoline resistance by downregulating ferroptosis in prolactinoma. J Endocrinol Invest. 2023 Aug;46(8):1573-1587. doi: 10.1007/s40618-023-02010-w. Epub 2023 Feb 28.
Ref 3 Antitumor effects of Andrographis via ferroptosis-associated genes in gastric cancer. Oncol Lett. 2021 Jul;22(1):523. doi: 10.3892/ol.2021.12784. Epub 2021 May 12.