General Information of the Ferroptosis Regulator (ID: REG10047)
Regulator Name Aquaporin-8 (AQP8)
Gene Name AQP8
Gene ID 343
Regulator Type Protein coding
Uniprot ID O94778
Sequence
MSGEIAMCEPEFGNDKAREPSVGGRWRVSWYERFVQPCLVELLGSALFIFIGCLSVIENG
TDTGLLQPALAHGLALGLVIATLGNISGGHFNPAVSLAAMLIGGLNLVMLLPYWVSQLLG
GMLGAALAKAVSPEERFWNASGAAFVTVQEQGQVAGALVAEIILTTLLALAVCMGAINEK
TKGPLAPFSIGFAVTVDILAGGPVSGGCMNPARAFGPAVVANHWNFHWIYWLGPLLAGLL
VGLLIRCFIGDGKTRLILKAR

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Family MIP/aquaporin family
Function
Channel that allows the facilitated permeation of water and uncharged molecules, such as hydrogen peroxide and the neutral form of ammonia (NH3), through cellular membranes such as plasma membrane, inner mitochondrial membrane and endoplasmic reticulum membrane of several tissues. The transport of the ammonia neutral form induces a parallel transport of proton, at alkaline pH when the concentration of ammonia is high. However, it is unclear whether the transport of proton takes place via the aquaporin or via an endogenous pathway. Also, may transport ammonia analogs such as formamide and methylamine, a transport favourited at basic pH due to the increase of unprotonated (neutral) form, which is expected to favor diffusion. Does not transport urea or glycerol. The water transport mechanism is mercury- and copper-sensitive and passive in response to osmotic driving forces. At the canicular plasma membrane, mediates the osmotic transport of water toward the bile canaliculus and facilitates the cAMP-induced bile canalicular water secretion, a process involved in bile formation. In addition, mediates the hydrogen peroxide release from hepatocyte mitochondria that modulates the SREBF2-mediated cholesterol synthesis and facilitates the mitochondrial ammonia uptake which is metabolized into urea, mainly under glucagon stimulation. In B cells, transports the CYBB- generated hydrogen peroxide from the external leaflet of the plasma membrane to the cytosol to promote B cell activation and differentiation for signal amplification. In the small intestine and colon system, mediates water transport through mitochondria and apical membrane of epithelial cells. May play an important role in the adaptive response of proximal tubule cells to acidosis possibly by facilitating the mitochondrial ammonia transport.

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HGNC ID
HGNC:642
KEGG ID hsa:343
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
AQP8 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).
Browse Target
Browse Disease
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Cytochrome b-245 heavy chain (CYBB) [Driver]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer ICD-11: 2C77
Responsed Drug Hydrogen Peroxide Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer ICD-11: 2C77
Responsed Drug Hydrogen Peroxide Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Cervical cancer [ICD-11: 2C77]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Aquaporin-8 (AQP8) Protein coding
Responsed Drug Hydrogen Peroxide Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Aquaporin-8 (AQP8) Protein coding
Responsed Drug Hydrogen Peroxide Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Hydrogen Peroxide [Investigative]
In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Cytochrome b-245 heavy chain (CYBB) Driver
Responsed Disease Cervical cancer ICD-11: 2C77
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 2 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Cytochrome b-245 heavy chain (CYBB) Driver
Responsed Disease Cervical cancer ICD-11: 2C77
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
References
Ref 1 Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis. Free Radic Biol Med. 2020 Dec;161:60-70. doi: 10.1016/j.freeradbiomed.2020.09.027. Epub 2020 Oct 2.