| 1998 |
AQP9 expressed in Xenopus oocytes functions as an osmotic water channel (7-fold increase in water permeability, low activation energy, mercury-inhibitable) and facilitates urea transport (4-fold increase), but does not increase glycerol permeability, distinguishing it from AQP3 and AQP7. |
Xenopus oocyte expression system, osmotic swelling assay, radiolabeled solute uptake |
Biochemical and biophysical research communications |
High |
9514918
|
| 2002 |
AQP9 (and AQP7) transport arsenite [As(III)] and antimonite [Sb(III)]: AQP9 expressed in yeast fps1Δ cells restores metalloid sensitivity and enhances (73)As(III) and (125)Sb(III) uptake; AQP7 and AQP9 cRNA-injected Xenopus oocytes show increased (73)As(III) transport. |
Yeast complementation of fps1Δ strain, radiolabeled metalloid uptake in yeast and Xenopus oocytes |
Proceedings of the National Academy of Sciences of the United States of America |
High |
11972053
|
| 2003 |
Purified rat AQP9 reconstituted in proteoliposomes exhibits mercury-inhibitable glycerol permeability (63-fold over background) and urea permeability (90-fold over background) at pH 7.5, but does not significantly increase beta-hydroxybutyrate or osmotic water permeability. AQP9 protein is localized to sinusoidal surfaces of hepatocyte plasma membranes, and its expression is induced up to 20-fold by fasting and elevated in streptozotocin-diabetic rats, returning to baseline with insulin treatment. |
Proteoliposome reconstitution with purified AQP9, stopped-flow light scattering, radiolabeled solute flux assays, confocal immunofluorescence, Western blot in fasted/diabetic rats |
Proceedings of the National Academy of Sciences of the United States of America |
High |
12594337
|
| 2004 |
AQP9 expression in K562 chronic myelogenous leukemia cells increases uptake of trivalent arsenic (As(III)) and antimonite (Sb(III)) and confers hypersensitivity to Trisenox (arsenic trioxide) and Sb(III). Vitamin D treatment of HL60 cells increases AQP9 expression and similarly confers metalloid hypersensitivity, demonstrating that AQP9 is the drug uptake transporter responsible for arsenic-based chemotherapy sensitivity. |
Stable transfection of AQP9 into K562 cells, cell viability assays, radiolabeled metalloid uptake, pharmacological induction with vitamin D |
Biochemical and biophysical research communications |
High |
15336539
|
| 2005 |
Brain mitochondria express a short (~25 kDa) AQP9 isoform arising from alternative splicing, which is enriched in the inner mitochondrial membrane as shown by subcellular fractionation and immunogold electron microscopy. This isoform is present in astrocytes throughout the brain and in dopaminergic neurons of substantia nigra, ventral tegmental area, and arcuate nucleus. |
Subcellular fractionation, immunoblotting, immunogold electron microscopy, double-labeling with tyrosine hydroxylase, in situ hybridization |
FASEB journal |
Medium |
16126913
|
| 2007 |
AQP9 knockout mice show markedly elevated plasma glycerol and triglycerides compared to wild-type, confirming AQP9's role as the primary hepatic entry channel for glycerol. Blood glucose was significantly lower in obese AQP9-knockout (Leprdb/Leprdb AQP9-/-) mice during fasting, indicating AQP9 is required for efficient hepatic glycerol utilization in gluconeogenesis. AQP9 protein was detected in hepatocytes, epididymis, vas deferens, and epidermis but not in brain. |
AQP9 knockout mouse phenotyping, plasma glycerol/triglyceride/glucose measurements, immunohistochemistry with multiple antibodies and knockout controls, oral glycerol tolerance test |
Proceedings of the National Academy of Sciences of the United States of America |
High |
17360690
|
| 2007 |
AQP9 expression in RGC-5 retinal ganglion cells mediates cell volume regulation in response to hypotonic stress; the AQP9 inhibitor phloretin blocks hypotonic-induced cell swelling. AQP9 expression is upregulated by hypoxia and hypotonic shock, suggesting a role in energy balance as a glycerol-lactate channel in retinal ganglion neurons. |
Cell volume measurement, pharmacological inhibition with phloretin, Western blot and RT-PCR under hypoxia/hypotonic conditions in RGC-5 cells and primary RGCs |
Pharmacological research |
Medium |
17337204
|
| 2007 |
In streptozotocin-diabetic rats (low systemic insulin), AQP9 expression is selectively increased in catecholaminergic neurons of the brainstem. In brainstem slice cultures, 2 μM insulin application significantly decreases AQP9 protein levels within 6 h, demonstrating direct insulin-mediated regulation of brain AQP9 in catecholaminergic neurons. |
Immunocytochemistry, Western blot, brainstem slice culture with insulin treatment |
Brain research |
Medium |
18053968
|
| 2009 |
AQP9 in brain exists in tetrameric form (confirmed by blue native gel electrophoresis); the tetramer band is absent in AQP9 knockout brain and liver. Subpopulations of nigral neurons express AQP9 at both mRNA and protein levels; cortical cells including hilar hippocampal neurons contain AQP9 mRNA but no detectable AQP9 immunosignal. |
Blue native PAGE, real-time PCR, immunocytochemistry, in situ hybridization, all with AQP9 knockout controls |
Journal of neuroscience research |
High |
19115411
|
| 2009 |
Human AQP9 transports pentavalent methylated arsenicals MAs(V) and DMAs(V) in a pH-dependent manner (higher rate at pH 5.5 than neutral pH) in Xenopus oocytes. Hg(II) inhibits all four arsenic species transport; phloretin inhibits pentavalent MAs(V) and DMAs(V) but not trivalent As(III) and MAs(III), indicating distinct translocation mechanisms for trivalent vs. pentavalent arsenicals through AQP9. |
Xenopus oocyte expression, radiolabeled arsenic uptake at different pH, pharmacological inhibition with Hg(II), phloretin, FCCP, valinomycin, nigericin |
Biometals |
High |
19802720
|
| 2009 |
CFTR co-localizes with AQP9 at the apical membrane of syncytiotrophoblast in normal placenta; CFTR expression decreases in preeclamptic placentas with loss of apical co-localization with AQP9. CFTR inhibitors reduce water uptake in normal placental explants, suggesting CFTR regulates AQP9 functionality. |
Western blot, immunohistochemistry, immunofluorescence co-localization, CFTR inhibitor functional water uptake assay in placental explants |
Placenta |
Medium |
19481256
|
| 2012 |
siRNA knockdown of AQP9 in cultured astrocytes decreases glycerol uptake and is associated with compensatory increase in glucose uptake and oxidative metabolism, confirming AQP9 as the primary glycerol transport pathway in astrocytes and demonstrating its role in astrocyte energy metabolism. |
AQP9 siRNA in astrocyte cultures, glycerol uptake assay, glucose uptake measurement, metabolic profiling |
Brain research |
Medium |
22842525
|
| 2013 |
Site-directed mutagenesis of an intracellular binding site on AQP9 (identified by homology modeling and molecular dynamics/docking) alters sensitivity to small molecule inhibitors, validating the intracellular binding site as functionally relevant. Novel inhibitors with low micromolar IC50 identified by in silico screening targeting this site are active in mammalian cell water permeability assays. |
Homology modeling, molecular dynamics simulation, molecular docking, site-directed mutagenesis, mammalian cell water permeability assay |
Molecular membrane biology |
Medium |
23448163
|
| 2014 |
AQP9 and monocarboxylate transporter MCT2 co-immunoprecipitate from hippocampal neuron homogenates and co-localize in mitochondria of hippocampal neurons. Glutamate exposure increases AQP9 and MCT2 protein expression post-translationally (no mRNA change), and decreases glucose utilization, suggesting AQP9 facilitates alternative fuel (monocarboxylate) access to mitochondria. |
Co-immunoprecipitation, co-localization imaging, Western blot and RT-PCR before/after glutamate treatment, glucose utilization assay in primary hippocampal neurons |
Frontiers in neuroscience |
Medium |
25161606
|
| 2018 |
AQP9 is permeable to the parkinsonogenic toxin MPP+ as demonstrated by Xenopus oocyte uptake assay. Stable AQP9 expression in HEK cells increases their vulnerability to MPP+ and arsenite. AQP9 knockout in mice protects nigral dopaminergic neurons from MPP+ toxicity in organotypic midbrain slice cultures and in vivo intrastriatal injection models (48% reduction in TH+ cells in AQP9 KO vs. 67% in WT). |
Xenopus oocyte MPP+ uptake assay, stable HEK cell expression, cell viability, organotypic slice culture, intrastriatal MPP+ injection in AQP9 KO vs. WT mice, TH+ cell counting |
PloS one |
High |
29566083
|
| 2020 |
AQP9 acts as an astrocyte-to-neuron lactate shuttle (ANLS) in concert with monocarboxylate transporters (MCTs) to support retinal ganglion cell (RGC) function and survival. AQP9 co-localizes with MCTs 1, 2, and 4 at the ganglion cell layer and co-immunoprecipitates with these MCTs in WT retina. Aqp9-null mice show greater RGC loss and reduced electroretinographic pSTR amplitude after optic nerve crush, reduced intraretinal lactate, and elevated glucose levels; glucose transporter GLUT1 expression is compensatorily increased. |
Aqp9 knockout mouse with optic nerve crush model, RGC density counting, electroretinography, co-immunoprecipitation of AQP9 with MCT1/2/4, immunolabeling, intraretinal metabolite measurement, MCT2 inhibitor injection |
Molecular neurobiology |
High |
32748371
|
| 2022 |
AQP9 transports lactate in macrophages: AQP9 overexpression in CHO cells increases lactate import rate; AQP9-/- macrophages and AQP9 knockdown RAW264.7 cells show reduced lactate transport. In the tumor microenvironment, AQP9-mediated lactate import drives M2-like macrophage polarization and VEGF production; AQP9-/- mice resist tumor growth and show suppressed M2 polarization in tumor tissue. |
AQP9 overexpression in CHO cells (lactate transport assay), AQP9-/- bone marrow-derived macrophage polarization assay, AQP9 knockdown in RAW264.7 cells, tumor allograft mouse model, VEGF ELISA |
Biochemistry and biophysics reports |
High |
35967760
|
| 2024 |
AQP9 in macrophages transports glycerol intracellularly where it is metabolized to lysophosphatidic acid (LPA), activating the LPAR2 receptor and downstream Hippo pathway to promote expression of cytokines IL-23 and IL-1β. AQP9 blockade in macrophages decreases inflamed macrophage cytokine expression and enhances anti-TNF therapy response in a CD mouse model. |
Transcriptomic analysis, AQP9-specific inhibition in macrophages, cytokine expression (ELISA, Western blot), LPA metabolite measurement, LPAR2 pathway mechanistic studies, in vivo CD mouse model |
Pharmacological research |
Medium |
38583685
|
| 2025 |
AQP9 knockdown in PMA-stimulated neutrophils suppresses JAK2-STAT3 pathway activation, reduces pyroptosis, and decreases NET formation, thereby reducing intestinal epithelial cell injury. Reactivation of JAK2-STAT3 or pyroptosis in AQP9-knockdown neutrophils restores NET formation and epithelial damage, placing AQP9 upstream of JAK2-STAT3-mediated pyroptosis in neutrophil-driven intestinal inflammation. |
siRNA knockdown of AQP9 in PMA-stimulated neutrophils, Western blot for JAK2-STAT3 pathway, ELISA for cytokines, immunofluorescence for NETs, co-culture with intestinal epithelial cells, CCK-8 and TUNEL assays, DSS-induced colitis mouse model |
Frontiers in bioscience (Landmark edition) |
Medium |
41504039
|
| 2025 |
Selective pharmacological blockade of AQP9 (with inhibitor RG100204) significantly impairs PBMC and neutrophil migration in response to LPS. Simultaneous inhibition of both AQP3 and AQP9 is required to impair monocyte phagocytosis of K. pneumoniae (at 60 min); individual AQP9 blockade alone does not affect bacterial killing. |
Specific AQP9 inhibitor (HTS13286 and RG100204) treatment of human PBMCs and neutrophils, transwell migration assay with/without LPS, phagocytosis assay with K. pneumoniae, bacterial killing assay, RT-qPCR, immunofluorescence |
Cells |
Medium |
40558507
|
| 2010 |
hCG treatment of normal placental explants increases AQP9 protein expression in a concentration-dependent manner via cAMP pathways (mimicked by 8-Br-cAMP), and increases water uptake 1.6-fold; AQP9 localizes to both the apical membrane and cytoplasm of syncytiotrophoblast after treatment. |
Placental explant culture with recombinant hCG or 8-Br-cAMP, Western blot, immunofluorescence localization, water uptake assay |
Reproductive sciences |
Medium |
20220109
|
| 2011 |
Insulin decreases AQP9 molecular expression in normal placental explants in a concentration-dependent manner; TNF-α pretreatment (which induces IRS phosphorylation and desensitizes insulin signaling) prevents insulin-induced AQP9 downregulation. Insulin treatment does not modify water uptake or its mercury sensitivity in placental explants, indicating AQP9 water permeability is independent of its expression level in this tissue. |
Placental explant culture with varying insulin concentrations, TNF-α pretreatment, Western blot for AQP9, water uptake assay with HgCl2 sensitivity |
Placenta |
Medium |
22018417
|