General Information of the Ferroptosis Target (ID: TAR10049)
Target Name Sodium-coupled neutral amino acid symporter 1 (SLC38A1)
Synonyms
Amino acid transporter A1; N-system amino acid transporter 2; Solute carrier family 38 member 1; System A amino acid transporter 1; System N amino acid transporter 1
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Gene Name SLC38A1
Sequence
MMHFKSGLELTELQNMTVPEDDNISNDSNDFTEVENGQINSKFISDRESRRSLTNSHLEK
KKCDEYIPGTTSLGMSVFNLSNAIMGSGILGLAFALANTGILLFLVLLTSVTLLSIYSIN
LLLICSKETGCMVYEKLGEQVFGTTGKFVIFGATSLQNTGAMLSYLFIVKNELPSAIKFL
MGKEETFSAWYVDGRVLVVIVTFGIILPLCLLKNLGYLGYTSGFSLSCMVFFLIVVIYKK
FQIPCIVPELNSTISANSTNADTCTPKYVTFNSKTVYALPTIAFAFVCHPSVLPIYSELK
DRSQKKMQMVSNISFFAMFVMYFLTAIFGYLTFYDNVQSDLLHKYQSKDDILILTVRLAV
IVAVILTVPVLFFTVRSSLFELAKKTKFNLCRHTVVTCILLVVINLLVIFIPSMKDIFGV
VGVTSANMLIFILPSSLYLKITDQDGDKGTQRIWAALFLGLGVLFSLVSIPLVIYDWACS
SSSDEGH

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Family Amino acid/polyamine transporter 2 family
Function
Symporter that cotransports short-chain neutral amino acids and sodium ions from the extraccellular to the intracellular side of the cell membrane . The transport is elctrogenic, pH dependent and driven by the Na(+) electrochemical gradient. Participates in the astroglia-derived glutamine transport into GABAergic interneurons for neurotransmitter GABA de novo synthesis. May also contributes to amino acid transport in placental trophoblasts. Also regulates synaptic plasticity.

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Gene ID 81539
Uniprot ID
Q9H2H9
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)
SLC38A1 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
ZFAS1 (IncRNA)
Pulmonary fibrosis [ICD-11: CB03]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
In Vitro Model
HFL1 cells Normal Homo sapiens CVCL_0298
In Vivo Model
Male Sprague-Dawley rats (200-220 g) were purchased from Weitonglihua Company (Beijing, China) and maintained in a pathogen-free facility. After one week of adaptive feeding, a total of 30 rats were randomly divided into 3 groups (n = 10 rats/group): a control group; bleomycin (BLM) group; and BLM + sh-ZFAS1 group. Rats in the BLM group were administered 5 mg/kg BLM (Nippon Kayaku, Japan) dissolved in phosphate buffered saline (PBS) and administered to the rats intratracheally to establish the PF model. Rats in the control group were treated with 0.05 mL PBS. Rats in the BLM + sh-ZFAS1 group were injected intraperitoneally with 30 uL lncRNA ZFAS1 shRNA adeno-associated virus 5 (Vigene Biosciences, USA) for 3 weeks prior to an injection of 5 mg/kg BLM sulfate.

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Response Description Inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and pulmonary fibrosis (PF) development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression.
OGFRP1 (IncRNA)
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
BEAS-2B cells Normal Homo sapiens CVCL_0168
In Vivo Model
Male nude mice (5-week-old) were purchased from Jinan Pengyue Animal Breeding Center (Jinan, China). Next, mice models were established by subcutaneously injecting A549 cells (1 x 106 cells/100 uL) into the right armpit flanks, which were stably transfected with sh-NC or sh-OGFRP1. Tumor formation was monitored and tumor volume was calculated every week for 5 weeks according to the formula: tumor volume = 1/2 (length x width2). Totally 35 days upon injection, the mice were euthanized and the tumors were dissected out from the right armpit flanks and weighted. The tumor tissues of nude mice with lung cancer were snap-frozen in liquid nitrogen immediately and stored at -80 for further research.

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Response Description OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer.
hsa-miR-299-3p (miRNA)
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
BEAS-2B cells Normal Homo sapiens CVCL_0168
In Vivo Model
Male nude mice (5-week-old) were purchased from Jinan Pengyue Animal Breeding Center (Jinan, China). Next, mice models were established by subcutaneously injecting A549 cells (1 x 106 cells/100 uL) into the right armpit flanks, which were stably transfected with sh-NC or sh-OGFRP1. Tumor formation was monitored and tumor volume was calculated every week for 5 weeks according to the formula: tumor volume = 1/2 (length x width2). Totally 35 days upon injection, the mice were euthanized and the tumors were dissected out from the right armpit flanks and weighted. The tumor tissues of nude mice with lung cancer were snap-frozen in liquid nitrogen immediately and stored at -80 for further research.

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Response Description OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer.
hsa-miR-150-5p (miRNA)
Pulmonary fibrosis [ICD-11: CB03]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
In Vitro Model
HFL1 cells Normal Homo sapiens CVCL_0298
In Vivo Model
Male Sprague-Dawley rats (200-220 g) were purchased from Weitonglihua Company (Beijing, China) and maintained in a pathogen-free facility. After one week of adaptive feeding, a total of 30 rats were randomly divided into 3 groups (n = 10 rats/group): a control group; bleomycin (BLM) group; and BLM + sh-ZFAS1 group. Rats in the BLM group were administered 5 mg/kg BLM (Nippon Kayaku, Japan) dissolved in phosphate buffered saline (PBS) and administered to the rats intratracheally to establish the PF model. Rats in the control group were treated with 0.05 mL PBS. Rats in the BLM + sh-ZFAS1 group were injected intraperitoneally with 30 uL lncRNA ZFAS1 shRNA adeno-associated virus 5 (Vigene Biosciences, USA) for 3 weeks prior to an injection of 5 mg/kg BLM sulfate.

    Click to Show/Hide
Response Description Inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and pulmonary fibrosis (PF) development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression.
Unspecific Regulator
Neurotoxicity [ICD-11: NE61]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Responsed Drug Formaldehyde Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

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Response Description Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
Unspecific Regulator
Formaldehyde [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Responsed Disease Neurotoxicity [ICD-11: NE61]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

    Click to Show/Hide
Response Description Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
References
Ref 1 lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis. Aging (Albany NY). 2020 May 26;12(10):9085-9102. doi: 10.18632/aging.103176. Epub 2020 May 26.
Ref 2 Long non-coding RNA OGFRP1 regulates cell proliferation and ferroptosis by miR-299-3p/SLC38A1 axis in lung cancer. Anticancer Drugs. 2022 Oct 1;33(9):826-839. doi: 10.1097/CAD.0000000000001328. Epub 2022 Aug 31.
Ref 3 Formaldehyde induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect. Toxicology. 2021 Jan 30;448:152650. doi: 10.1016/j.tox.2020.152650. Epub 2020 Nov 28.