Overexpression Of Aquaporin Research Articles

Tobacco aquaporin NtAQP1 and human aquaporin hAQP1 contribute to single cell photosynthesis in Synechococcus.

Aquaporins are H2O-permeable membrane protein pores. However, some aquaporins are also permeable to other substances such as CO2. In higher plants, overexpression of such aquaporins has already led to an enhanced photosynthetic performance due to improved CO2 mesophyll conductance. In this work, we investigated the effects of such aquaporins on unicellular photosynthetically active organisms, specifically cyanobacteria. Overexpression of aquaporins NtAQP1 or hAQP1 that might have a function to improve CO2 membrane permeability lead to increased photosynthesis rates in the cyanobacterium Synechococcus sp. PCC7002 as concluded by the rate of evolved O2. A shift in the Plastoquinone pool state of the cells supports our findings. Water permeable aquaporins without CO2 permeability, such as NtPIP2;1, do not have this effect. We conclude that also in single cell organisms like cyanobacteria, membrane CO2 conductivity could be rate limiting and CO2-porins reduce the respective membrane resistance. We could show that besides the tobacco aquaporin NtAQP1 also the human hAQP1 most likely functions as CO2 diffusion facilitator in the photosynthesis assay.

Lychee Pulp-Derived Dietary Fiber-Bound Phenolic Complex Upregulates the SCFAs-GPRs-ENS Pathway and Aquaporins in Loperamide-Induced Constipated Mice by Reshaping Gut Microbiome.

This study aimed to investigate the effects of the lychee pulp-derived dietary fiber-bound phenolic complex (DF-BPC) on a murine model of loperamide-induced constipation and its molecular mechanism associated with gut microbiota modification. DF-BPC supplementation mitigated loperamide-induced dyschezia, intestinal hypomotility, and colonic impairment, as evidenced by the increased gastro-intestinal transit rate and mucus cell counts. By comparison, short-chain fatty acids (SCFAs) contents and relative abundances of associated genera (Butyricimonas, Clostridium, and Lactobacillus) were effectively upregulated following DF-BPC supplementation. Notably, DF-BPC significantly enhanced expressions of G protein-coupled receptor (GPR) 41 and 43, reaching 1.43- and 1.62-fold increase, respectively. Neurotransmitter secretions were simultaneously altered in DF-BPC-treated mice, suggesting upregulation of the SCFAs-GPRs-enteric nervous system pathway. The overexpression of aquaporins (AQP3, 8, and 9) was stimulated partly through GPRs activation. Mild inflammation associated with constipation was inhibited by suppressing LBP-TLR4-NF-κB signaling translocation. These findings suggest that DF-BPC from lychee pulp has the potential to alleviate constipation in mice through modifying the gut microbiome.

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study.

Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

Molecular dynamics simulation of the effect of AQP1 on the transmembrane transport of plasma RONS across cancer cell membranes

In the cold atmospheric plasma (CAP)-assisted cancer treatment, the increase in the concentration of reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by CAP is believed to be related to the overexpression of aquaporins (AQPs) on cancer cell membranes. In this paper, using classical molecular dynamics simulations, the transmembrane behavior of RNS and ROS on a pure phospholipid bilayer or a AQP1-phospholipid bilayer model was studied. The research shows that hydrophobic RNS tend to be transported through the bilayer of phospholipids. The overexpression of AQP1 can significantly improve the transmembrane efficiency of hydrophilic ROS. Our simulation fills the gap in the research for RNS-related molecular simulation and provides guidance for the precise targeting of cancer cells in CAP therapy.

Relationship between ionomics and transcriptomics of rice plant in response to arsenite stress

Paddy rice cultivated in flooded fields tends to accumulate more arsenic than other terrestrial crops. Ionomic profiling and transcriptomic variations of rice plants were investigated to understand the molecular mechanism used to counteract arsenite [As(III)] stress. The total concentrations of 29 elements in the rice shoots and roots under control and As(III) stress conditions were determined by inductively coupled plasma mass spectrometry (ICP-MS). Ionomic differences between rice tissues under different conditions were identified through principal component analysis. Compared to their external conditions, the genomic composition plays a more important role in rice ionomics. In the transcriptome analyses, a total of 3812 differentially expressed genes (DEGs) were identified in the As(III)-treated shoots compared to the control shoots. The significant DEGs generated by gene ontology enrichment analysis were mainly associated with transmembrane transporters and ion binding, which were directly correlated with ionomics. Upregulation of transporter genes correlated with nutrient elements was observed, indicating that the rice plants tended to translocate more nutrients, such as potassium, phosphate and ammonium, to cope with As(III) toxicity. Transcriptomics also showed overexpression of aquaporins and ABC transporters for detoxification of As(III) in rice plants. Further investigation is necessary for a deeper insight into the molecular mechanism involved in the ionomics of rice plants.

Overexpression of aquaporin 2 in renal tubular epithelial cells alleviates pyroptosis.

BackgroundSevere renal ischemia-reperfusion injury results in worse outcomes of kidney transplantation. Compared to the collecting duct, the proximal tubule is more likely to exhibit severe pyroptosis and damage during renal ischemia-reperfusion. Aquaporins were reported of having regulatory roles in pyroptosis. We explored whether aquaporin 2 overexpression in proximal tubular cells could alleviate ischemia-reperfusion injury related pyroptosis.MethodsA renal ischemia-reperfusion model of mice was established, and human kidney 2 cells were treated with hypoxia-reoxygenation. Aquaporin 2 overexpression was achieved in human kidney 2 cells transfected with lentivirus, which were then cultured with murine cells. Renal tissues and serum of the mice, and human kidney 2 cells were subjected to histological, molecular, and biochemical examinations.ResultsCompared with the sham group, the renal function of the ischemia-reperfusion group was significantly decreased, and the tissue injury was severe and accompanied by more nuclear dissolved and necrosis. Besides, the expression of aquaporin 1-5 decreased significantly, while the expression of Toll-like receptor 4, caspase-1, kim-1 and interleukin 1β and 18 increased significantly in ischemia-reperfusion group. Similar results were observed in the human kidney 2 cells test. Overexpression of aquaporin 2 partially reversed the cell damage, pyroptosis, and molecular expression changes of human kidney 2 cells induced by hypoxia-reoxygenation.ConclusionsOur findings suggest that aquaporin 2 overexpression can potentially reduce pyroptosis in proximal tubular cells, and thus might be a novel target for relieving pyroptosis and injury in renal ischemia-reperfusion injury.

The Role of Aquaporin Overexpression in the Modulation of Transcription of Heavy Metal Transporters under Cadmium Treatment in Poplar.

Populus alba ‘Villafranca’ clone is well-known for its tolerance to cadmium (Cd). To determine the mechanisms of Cd tolerance of this species, wild-type (wt) plants were compared with transgenic plants over-expressing an aquaporin (aqua1, GenBank GQ918138). Plants were maintained in hydroponic conditions with Hoagland’s solution and treated with 10 µM of Cd, renewed every 5 d. The transcription levels of heavy metal transporter genes (PaHMA2, PaNRAMP1.3, PaNRAMP2, PaNRAMP3.1, PaNRAMP3.2, PaABCC9, and PaABCC13) were analyzed at 1, 7, and 60 d of treatment. Cd application did not induce visible toxicity symptoms in wt and aqua1 plants even after 2 months of treatment confirming the high tolerance of this poplar species to Cd. Most of the analyzed genes showed in wt plants a quick response in transcription at 1 d of treatment and an adaptation at 60 d. On the contrary, a lower transcriptional response was observed in aqua1 plants in concomitance with a higher Cd concentration in medial leaves. Moreover, PaHMA2 showed at 1 d an opposite trend within organs since it was up-regulated in root and stem of wt plants and in leaves of aqua1 plants. In summary, aqua1 overexpression in poplar improved Cd translocation suggesting a lower Cd sensitivity of aqua1 plants. This different response might be due to a different transcription of PaNRAMP3 genes that were more transcribed in wt line because of the importance of this gene in Cd compartmentalization.

Overexpression of Aquaporin 1 in Synovium Aggravates Rat Collagen-Induced Arthritis Through Regulating β-Catenin Signaling: An in vivo and in vitro Study.

IntroductionPrevious studies have confirmed that aquaporin 1 (AQP1) is up-regulated in synovium of rheumatoid arthritis (RA), but its exact pathogenic mechanisms in RA are unclear. This study revealed the pathogenic role of AQP1 in rat collagen-induced arthritis (CIA) and the underlying mechanisms related to β-catenin signaling.Materials and MethodsSecondary paw swelling and pathological changes of ankle joints were used to evaluate the severity of rat CIA. Synovial AQP1 and β-catenin expression were measured by immunohistochemistry (IHC) and Western blot assay. AQP1 siRNA was applied to knockdown AQP1 in cultured CIA fibroblast-like synoviocyte (FLS). Assays of MTT, PCNA immunofluorescence and transwell were performed to detect cell proliferation, migration and invasion. The protein levels of β-catenin pathway members and ratio of TOP/FOP luciferase activity were also measured.ResultsIn vivo, we revealed that synovial AQP1 and β-catenin expressions in CIA rats were higher than normal rats, and synovial AQP1 expression of CIA rats increased in parallel with secondary paw swelling and total pathological score on joint damage. Correlation analysis of IHC results indicated that synovial AQP1 expression positively correlated with β-catenin expression in CIA rat. In vitro, AQP1 siRNA apparently reduced the proliferation, migration and invasion of CIA FLS by inhibiting β-catenin signaling pathway. As an activator of β-catenin signaling, lithium chloride (an inhibitor of GSK-3β) reversed the inhibitory effects of AQP1 siRNA on the cultured CIA FLS.ConclusionWe concluded that the overexpression of synovial AQP1 aggravated rat CIA by promoting the activation of FLS through β-catenin signaling pathway.

Humic acids and Herbaspirillum seropedicae change the extracellular H+ flux and gene expression in maize roots seedlings

BackgroundThe use of plant-based biostimulants to increase crop yield and enhance protection has grown in popularity. We previously manufactured an inoculant combining humic acids with plant growth-promoting bacteria and observed a significant effect on crop yields. However, electrophysiology studies elucidating the mechanisms responsible for enhanced nutrient and water uptake are scarce and are generally restricted to in vitro models.Materials and methodsIn this study, a suspension of humic acids isolated from vermicompost along with Herbaspirillum seropedicae was applied to maize seedlings. We measured the root H+ flux with an ion-selective vibrating probe system. Furthermore, the transcription of plasma membrane H+ ATPase, aquaporin and high- or low-affinity nitrate transporters was measured.ResultsInoculation activated the extracellular H+ flux, thus changing the pH and membrane potential of maize root cells and altering the electrochemical potential generated by P–H+-ATPase at the biochemical and molecular level. The overexpression of aquaporins was also observed; however, nitrate transporters were repressed by the inoculants.ConclusionWe demonstrate an increase in the H+ efflux in maize root seedlings inoculated with H. seropedicae and concomitant changes in membrane voltage. The inoculation of H. seropedicae in the presence of humic acids decreased the H+ flux and surface acidification without changes in the aquaporin transcription level. However, the H+ flux in root seedlings in inoculated plants (with or without humic acids) was larger in respect to control plants. These results support the increased water and nitrogen efficiency in plants inoculated with humic acids and H. seropedicae.

Steviol slows renal cyst growth by reducing AQP2 expression and promoting AQP2 degradation

Overexpression of aquaporin 2 (AQP2) was observed and suggested to be involved in fluid secretion leading to cyst enlargement in polycystic kidney disease (PKD). The cyst expansion deteriorates the renal function and, therefore, therapies targeting cyst enlargement are of clinical interest. Of note, inhibition of vasopressin function using vasopressin 2 receptor (V2R) antagonist which decreased cAMP production along with AQP2 production and function can slow cyst growth in ADPKD. This finding supports the role of AQP2 in cyst enlargement. Steviol, a major metabolite of the sweetening compound stevioside, was reported to retard MDCK cyst growth and enlargement by inhibiting CFTR activity. Interestingly, its efficacy was found to be higher than that of CFTRinh-172. Since steviol was also found to produce diuresis in rodent, it is likely that steviol might have an additional effect in retarding cyst progression, such as inhibition of AQP2 expression and function. Here, we investigated the effect of steviol on AQP2 function and on cyst growth using an in vitro cyst model (MDCK and Pkd1−/− cells). We found that steviol could markedly inhibit cyst growth by reducing AQP2 expression in both Pkd1−/− and MDCK cells. Real-time PCR also revealed that steviol decreased AQP2 mRNA expression level as well. Moreover, a proteasome inhibitor, MG-132, and the lysosomotropic agent, hydroxychloroquine (HCQ) were found to abolish the inhibitory effect of steviol in Pkd1−/− cells. Increased lysosomal enzyme marker (LAMP2) expression following steviol treatment clearly confirmed the involvement of lysosomes in steviol action. In conclusion, our finding showed for the first time that steviol slowed cyst growth, in part, by reducing AQP2 transcription, promoted proteasome, and lysosome-mediated AQP2 degradation. Due to its multiple actions, steviol is a promising compound for further development in the treatment of PKD.

Overexpression of aquaporin 4 in articular chondrocytes exacerbates the severity of adjuvant-induced arthritis in rats: an in vivo and in vitro study

BackgroundThe dysfunction of articular chondrocytes is a crucial step in rheumatoid arthritis (RA) pathogenesis while its molecular mechanisms are not fully known. This study was aimed to investigate the expression of aquaporin 4 (AQP4) in articular chondrocytes of adjuvant-induced arthritis (AIA) rats and its involvement in AIA development.MethodsThirty rats were divided into normal and AIA group (n = 15). Rat AIA was induced by intradermal injection of complete Freund’s adjuvant and evaluated by secondary paw swelling and histological assessments on knee joint damage. Localization and protein expression of AQP4 in articular cartilage were examined by immunohistochemistry and western blot. In vitro study, AIA articular chondrocytes were cultured and treated with acetazolamide, an AQPs inhibitor. AQP4 protein level, cell proliferation and mRNA levels of type-II collagen (COII) and aggrecan were measured by western blot, MTT assay and real-time PCR, respectively.ResultsThe results of immunohistochemistry and western blot indicated that AQP4 showed higher protein levels in cartilage tissues of AIA rats than that of normal rats. Correlation analysis revealed that AQP4 protein level in cartilage tissues of AIA rats remarkably correlated positively with secondary paw swelling on day 26 after AIA induction as well as pathological scores on joint damage. Additionally, acetazolamide treatment effectively decreased AQP4 protein level, increased cell proliferation and mRNA levels of COII and aggrecan, suggesting AQP4 inhibition by acetazolamide could normalize the dysfunction of AIA articular chondrocytes in vitro.ConclusionsOur data provide certain experimental evidence that AQP4 over-expression in articular chondrocytes aggravated AIA severity and might be a novel target for RA treatment.

Non-invasive imaging using reporter genes altering cellular water permeability.

Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

Overexpression of Aquaporin 1 on cysts of patients with polycystic liver disease

Polycystic liver disease (PCLD) represents a group of genetic disorders that include autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (iPCLD). There is currently no definitive treatment except for liver transplantation. The aim of this study was to assess the expression level of aquaporin 1 (AQP1) on the PCLD cysts with different sizes and provide the potential therapeutic target. We collected 3 normal bile ducts, and recruited 8 patients with simple liver cyst disease, 24 patients with ADPKD, and 17 patients with iPCLD. AQP1 expression in different types of cyst walls and in normal bile ducts was detected using real time quantitative PCR, western blot and immunofluorescence staining. We also compared AQP1 expression levels in cysts of different sizes. Besides, ionic concentrations, pH and osmolality of cyst fluid were analyzed. The results showed that AQP1 expression in PCLD cysts was significantly higher than that in simple liver cysts and the normal bile ducts. In addition, a comparable increasing trend was found in cysts of smaller sizes to cysts of larger sizes. pH values, the sodium and chloride concentrations were higher in cyst fluid than that in the serum. AQP1 was overexpressed in cystic cholangiocytes. A tendency of increased AQP1 protein expression in correlation with the cyst size was also found. These observations offered a direction into the molecular mechanisms of cyst expansion and maybe provide new treatment strategies to reduce fluid secretion into liver cysts.

Aquaporin 8 involvement in human cervical cancer SiHa migration via the EGFR-Erk1/2 pathway.

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48 h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

683 Overexpression of aquaporin 2 and caveolin 1-3 in detrusor muscle of rat urinary bladder following bladder outlet obstruction

683 Overexpression of aquaporin 2 and caveolin 1-3 in detrusor muscle of rat urinary bladder following bladder outlet obstruction

Overexpression of aquaporin 1 in the tunica vaginalis may contribute to adult-onset primary hydrocele testis.

To investigate the cause of the adult-onset primary noncommunicating hydrocele testis, protein expressions of water channel aquaporins (AQPs) 1 and 3 in the tunica vaginalis were assessed. Frozen tunica vaginalis specimens from patients with adult-onset primary hydrocele testis and control male nonhydrocele patients were subjected to Western blot analysis for the detection of AQP1 and AQP3 proteins. Paraffin-embedded sections of tunica vaginalis specimens were histochemically stained with anti-AQP1 and anti-AQP3 antibodies as well as an anti-podoplanin antibody to stain lymphatic endothelia. Hydrocele fluid was subjected to biochemical analysis. AQP1 protein expression in the tunica vaginalis was significantly higher in patients with adult-onset hydrocele testis than in the controls. The AQP3 protein was not detected in the tunica vaginalis. Histochemically, AQP1 expression in the tunica vaginalis was localized in vascular endothelial and smooth muscle cells. The densities of AQP1-expressing capillaries and lymphatic vessels were similar between the tunica vaginalis of the controls and those of hydrocele patients. Sodium levels were higher in the hydrocele fluid than in the serum. In conclusion, overexpression of the AQP1 protein in individual capillary endothelial cells of the tunica vaginalis may contribute to the development of adult-onset primary noncommunicating hydrocele testis as another aquaporin-related disease.

Cellular overexpression of Aquaporins slows down the natural HIF-2α degradation during prolonged hypoxia

Overexpression of cell membrane aquaporins (AQPs) has recently been associated with tumor formation, particularly with angiogenesis, cell migration and proliferation. Additionally, the hypoxia inducible factor (HIF) family has been extensively implicated in tumor growth and recent studies evidence interplay between AQP expression and HIF stability. Therefore, we decided to explore the effect that AQP overexpression has on the long-term stability of HIF-2α in PC12 cells exposed to chronic hypoxia, characteristic of a growing tumor. HIF-2α levels were analyzed in five PC12 clones with stable overexpression of different proteins (AQP1, AQP3, AQP5, G6PD, and GDNF), in PC12 transiently expressing G6PD or Kv4.2, and in wild-type PC12 cells. Overexpression of AQP1, 3 or 5 in PC12 cells (o-AQP-c) prevented the HIF-2α down-expression otherwise observed, after 16h at 1% O2, in wt-PC12 and in PC12 overexpressing non-AQP proteins. Longer HIF-2α stability was also observed in o-AQP-c exposed to cobalt chloride or dimethyloxallyl glycine. Normal proteasome activity was confirmed in all clones analyzed. Levels of HIF target genes (PHD2 and 3, VEGF, and PGK1) were 2–4 fold higher in hypoxic o-AQP-c than in wt-PC12 cells, and morphological changes in colony shape together with higher cell proliferation rates were observed in all o-AQP-c. Interestingly, analysis of PHD levels under normoxia revealed lower (50%) PHD3 expression in o-AQP-c than in controls. Our results indicate that AQP overexpression in PC12 cells prolongs HIF-2α stability during chronic hypoxia, leading to higher level of induction of its target genes and likely conferring to these cells a more tumor-like phenotype.

Relationship of aquaporin 1, 3, and 5 expression in lung cancer cells to cellular differentiation, invasive growth, and metastasis potential

An oncogenic capacity of aquaporins, transmembrane channels for water, was recently proposed. This study seeks to elucidate the involvement of aquaporin 1, 3, and 5 in the development and progression of lung cancer. Expression of aquaporin 1, 3, and 5 was examined by immunohistochemistry, Western blot, and laser-captured microdissection/real-time reverse transcription polymerase chain reaction in 160 lung cancers of various histologic subtypes; and its correlation with clinicopathological factors and survival was analyzed. Aquaporin 1, 3, and 5 were expressed in tumor cells in 71%, 40%, and 56% of lung cancers, respectively. Aquaporin expressions were frequent in adenocarcinomas, whereas aquaporin 1 and 5 were negative in squamous cell carcinomas. Bronchioloalveolar carcinoma cells exhibited an apicolateral aquaporin 1 and apicolateral or basolateral aquaporin 3 localization in nonmucinous type, and apical aquaporin 1 and 5 and basolateral aquaporin 3 expression in mucinous type, which corresponded to aquaporins expression of nonneoplastic lung tissue. Basolateral aquaporin 5 expression was acquired during tumorigenesis of nonmucinous bronchioloalveolar carcinoma. In contrast, invasive adenocarcinoma tumor cells overexpressed aquaporin 1 and 5 with loss of subcellular polarization and with an intracytoplasmic distribution. Overexpression of aquaporin 1 correlated with high postoperative adenocarcinoma metastasis ratios and unfavorable disease-free survival rates (P = .031). We conclude that expression patterns of aquaporin 1, 3, and 5 in lung cancer cells are mostly associated with cellular differentiation. However, the expression of aquaporin 1 and 5 is up-regulated in invading lung cancer cells, particularly in adenocarcinomas; and the overexpression of aquaporin 1 with loss of subcellular polarization is suggested to be involved in their invasive and metastatic potential.

Aquaporin 1 and aquaporin 4 overexpression in bovine spongiform encephalopathy in a transgenic murine model and in cattle field cases

Aquaporins (AQP) are a family of transmembrane proteins that act as water selective channels. AQP1 and AQP4 are widely expressed in the central nervous system where they play several roles. Overexpression of AQP has been reported in some human and animal transmissible spongiform encephalopathies, but information is scanty about their distribution in the central nervous system in bovine spongiform encephalopathy (BSE). Double immunohistochemistry for AQP1, AQP4 and GFAP was developed in a transgenic mouse line overexpressing the bovine cellular prion protein (BoTg110), intracerebrally infected with cattle BSE. Western blot for AQP1 and AQP4, and immunohistochemistry for both AQP and GFAP were carried out in cases of BSE-diagnosed cattle as part of surveillance plan in Catalonia (Spain). A marked increase in AQP1 and AQP4 was observed in mice at the terminal stage of the disease, when they had a wide range of clinical signs, whereas no increase could be observed in the early stage before the onset of the clinical signs. In cattle which did not show evidence of clinical signs, both AQP already showed a great increase. The AQP overexpression correlated with GFAP-immunoreactive astrocytes and PrPres deposition in both cases. The results of this study suggest that AQP overexpression in glial cells could lead to an imbalance in water and ion homeostasis which could contribute to triggering the typical histopathological changes of BSE.

Skeletal muscle regeneration may be enhanced by overexpression of aquaporin 1 in intramuscular capillary endothelial cells

The article introduces the hypothesis that aquaporin 1 of intramuscular capillary endothelial cells may enhance the capability of the skeletal myofiber regeneration. Evidence for the hypothesis is based on the indication obtained from our previous muscle xenograft study into athymic nude mice, and the indications proposed by other investigators. (1) The transplanted human muscle xenografts contained the highly vascularized peripheral portions where the active regenerating myotubes were observed; while the central portions of the transplanted xenografts contained few capillaries and scarce regenerating myotubes. (2) Capillary endothelial cells in endomysium contained aquaporin 1 molecule at their cell membranes. (3) Aquaporin 1 molecule is proposed to function in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, organ regeneration and tumor growth and spread. Based on these indications the skeletal muscle regeneration may be enhanced by aquaporin 1 of intramuscular capillary endothelial cells. If verified, this new concept may lead to novel pharmaceutical or genetic approaches to the new treatments of intractable muscle diseases.