Disease relevance of AQP9

• AQP9 was transfected into the chronic myelogenous leukemia cell line K562 [1].
• Trisenox hypersensitivity results from increased expression of AQP9 drug uptake system [1].
• Q-PCR showed that primary APL cells expressed AQP9 significantly (2-3 logs) higher than other acute myeloid leukemias (AMLs), which might explain their exquisite As(2)O(3) sensitivity [2].
• In 10 of 11 myeloid and lymphoid leukemia lines, quantitative polymerase chain reaction (Q-PCR) and Western blotting showed that AQP9 expression correlated positively with As(2)O(3)-induced cytotoxicity [2].
• As a proof-of-principle, transfection of EGFP-tagged AQP9 to the hepatoma line Hep3B, not expressing AQP9 and As(2)O(3) insensitive, led to membrane AQP9 expression and increased As(2)O(3)-induced cytotoxicity [2].

High impact information on AQP9

• Multifunctional aquaglyceroporins AQP3, AQP7, and AQP9 are permeated by water, glycerol, and some other solutes [3].
• AQP9 is associated with elevated levels of active Cdc42 and filopodia formation [4]
• AQP9 plays an active role in neutrophil volume regulation and migration. The display of AQP9 at the plasma membrane depends on AQP9 phosphorylation, which appeared to be regulated through a Rac1-dependent pathway. [5]
• Similarly, the chronic myeloid leukemia line K562 expressed low levels of AQP9 and was As(2)O(3) insensitive [2].
• Little AQP7 or AQP9 mRNA was detected by reverse transcription-PCR in either cell line, whereas AQP3 mRNA expression was 2-fold lower in R15 cells than in CL3 cells [6].
• AQP9 mediates passage of a wide variety of non-charged solutes including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercury-sensitive manner, whereas amino acids, cyclic sugars, Na+, K+, Cl-, and deprotonated monocarboxylates are excluded [7].
• Unique expression and localization of aquaporin-4 and aquaporin-9 in murine and human neural stem cells and in their glial progeny [8].

Chemical compound and disease context of AQP9

• Pretreatment of the myeloid leukemia line HL-60 with all-trans retinoic acid (ATRA) up-regulated AQP9, leading to a significantly increased arsenic uptake and As(2)O(3)-induced cytotoxicity on incubation with As(2)O(3), which might explain the synergism between ATRA and As(2)O(3) [2].

Biological context of AQP9

• The human AQP9 gene is composed of 6 exons and 5 introns distributed over approximately approximately 25 kb [9].
• The promoter region contains putative tonicity and glucocorticoid-responsive elements, suggesting that AQP9 may be regulated by osmolality and catabolism [9].
• Here we report a reevaluation of the functional characteristics of hAQP9, its tissue distribution, the structure of its gene, and its chromosomal localization [9].
• A human homolog (hAQP9) with 76% amino acid sequence identity to rat AQP9 (rAQP9) was described, but its permeability was found to be restricted to water and urea (K. Ishibashi, M. Kuwahara, Y. Gu, Y. Tanaka, F. Marumo, and S. Sasaki. Biochem. Biophys. Res. Commun. 244: 268-274, 1998) [9].
• Insulin alone had no discernable influence on AQP9 gene expression or its cellular protein levels [10].

Anatomical context of AQP9

• AQP9 is enriched on the apical (but not basolateral) membrane of nonciliated cells in the efferent duct and principal cells of the epididymis (rat and human) and vas deferens, where it could play a role in fluid reabsorption [11].
• Intracellular vesicles in epithelial cells along the reproductive tract were generally poorly stained for AQP9 [11].
• AQP9 was detectable in the epididymis and vas deferens of 1-wk postnatal rats, but its expression was comparable with adult rats only after 3--4 wk [11].
• Furthermore, the apical membrane distribution of AQP9 was unaffected by microtubule disruption [11].
• AQP9 is also expressed in epithelial cells of the prostate and coagulating gland where fluid transport across the epithelium is important for secretory activity [11].

Associations of AQP9 with chemical compounds

• When expressed in Xenopus oocytes, hAQP9 allowed passage of a wide variety of noncharged solutes, including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercurial-sensitive manner [9].
• 3-beta-diol injections restored AQP9 expression, similar to DHT and estradiol [12].
• AQP9 displays unique hormonal regulation in the efferent ductules and epididymis, as it is regulated by both estrogen and dihydrotestosterone (DHT) in the efferent ductules, but only by DHT in the initial segment epididymis [12].
• A molecular analysis indicated lack of expression of aquaporin 9, thus excluding its involvement in the membrane translocation of cisplatin [13].

Other interactions of AQP9

• The promyelocytic leukemia cell line HL60 treated with vitamin D showed higher expression of AQP9 and hypersensitivity to Trisenox and Sb(III) [1].

Analytical, diagnostic and therapeutic context of AQP9

• Based on Northern blot analysis, both rat and human AQP9 are abundantly expressed in liver, whereas, in contrast to rAQP9, hAQP9 is also expressed in peripheral leukocytes and in tissues that accumulate leukocytes, such as lung, spleen, and bone marrow [9].
• RESULTS: Data show that, after castration, AQP9 expression was significantly reduced in the efferent ductules [12].
• Changes in AQP9 expression in the efferent ductules were investigated by using immunohistochemistry and Western blotting assay [12].
• Systems for gene transfer and silencing in human skeletal stem cells (hSSCs, also stromal or mesenchymal stem cells) are important for addressing critical issues in basic hSSC and skeletal biology and for developing gene therapy strategies for treatment of skeletal diseases [14].

References