Inhibition of Aquaporin-3 Water Channel in the Colon Induces Diarrhea

Ikarashi, Nobutomo; Kon, Risako; Iizasa, Tomohiko; Suzuki, Noriko; Hiruma, Reiko; Suenaga, Kiyomi; Toda, Takahiro; Ishii, Makoto; Hoshino, Motohiro; Ochiai, Wataru; Sugiyama, Kiyoshi

doi:10.1248/bpb.35.957

Cited by 55 publications

(36 citation statements)

References 33 publications

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“…AQP3 is considered to play an important role in regulating the colonic water movement. Previously, it has been demonstrated that the HgCl 2 rectal instillation affected AQP3 functioning in the colon and caused diarrhea, as fecal water content increased in mercurytreated rats about four times in comparison with controls (Ikarashi et al, 2012). In addition to the proper function of AQP3, some studies revealed a new and important function in enterocyte proliferation.…”

Section: Discussionmentioning

confidence: 99%

Impaired aquaporins expression in the gastrointestinal tract of rat after mercury exposure

Bottino

Vázquez

Devesa

et al. 2015

J of Applied Toxicology

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The main route of exposure to mercury in humans is through the diet. Consequently, the gastrointestinal mucosa is exposed to the mercurial forms, where they cause intestinal fluid accumulation, mucosal injuries and diarrhea. The relationship between inorganic mercury (HgCl2 ) and methylmercury (CH3 HgCl) exposure and water movement in the gastrointestinal tract is still unexplored. The leading role of aquaporins (AQPs) in the rapid bidirectional movement of fluid in the gastrointestinal tract of mammals is well established. The present study evaluates the effect of HgCl2 and CH3 HgCl exposure on AQP expression in different portions of the gastrointestinal tract of rats treated by gavage (5 mg kg(-1) of mercury species, single dose, 4 days). The results show that mercury species reduce mRNA and protein levels of AQPs in different parts of the gastrointestinal tract. In the stomach, treated rats show a significant reduction of expression of AQP3 (80-90% for mRNA and 50% for protein) and AQP4 (95-99% for mRNA and 20-40% for protein). In the small and large intestine, treated rats experience a significant reduction of AQP3 and AQP7 expression. Protein contents of both AQPs are reduced in similar proportions in jejunum (AQP3: 40-50%; AQP7: 45-50%) and colon (AQP3: 35-40%; AQP7: 45-60%), regardless of the treatment. Our results indicate that some AQPs are downregulated in the rat gastrointestinal tract by mercury exposure, suggesting a possible role of AQPs in the development of mercury gastrointestinal symptoms.

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Section: Discussionmentioning

confidence: 99%

Impaired aquaporins expression in the gastrointestinal tract of rat after mercury exposure

Bottino

Vázquez

Devesa

et al. 2015

J of Applied Toxicology

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“…Detailed procedures have been previously described [12]. Briefly, fecal samples from the mice were collected for up to 5 h after the administration of the MgSO 4 solutions and were placed in silica gel followed by drying for 48 h in a desiccator.…”

Section: Methodsmentioning

confidence: 99%

Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model

Zheng

Wang

et al. 2014

BioMed Research International

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Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4 in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunits α (PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expression in vivo and in vitro via downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE.

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“…Several studies have displayed the importance of AQPs in faecal concentration/water absorption in the colon. In a study on rats the inhibition of the AQP3 was shown to cause watery diarrhoea [201] and during exposure to mercury, the common inhibitor of AQPs, both AQP3 and 4 as well as 7 were downregulated and therefore believed to be involved in the mechanism of mercury-induced toxicity and gastrointestinal symptoms [202]. Wang et al also showed that AQP4 knockout mice demonstrated a higher water content in faeces [203].…”

Section: Aquaporins In Gastrointestinal Homeostasis and Diarrhoeamentioning

confidence: 99%

Aquaporins in Infection and Inflammation

Holm¹

2016

Linköping University Medical Dissertations

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About the cover:The front cover displays a human, blood-derived macrophage stained for aquaporin 9.During the course of the research underlying this thesis, Angelika Holm was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University Printed by LiU-Tryck, Linköping, Sweden, 2016 "Be brave, even if you're not, pretend to be. No one can tell the difference."To that young, awkward, tall girl who dared to dream of something else, something more:You did it. SUPERVISOR Elena VikströmDepartment of Clinical and Experimental Medicine Linköping University Linköping Sweden When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI-mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3O-C12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. ASSISTANT SUPERVISORS Karl-Eric MagnussonViruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulatio...

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Inhibition of Aquaporin-3 Water Channel in the Colon Induces Diarrhea

Cited by 55 publications

References 33 publications

Impaired aquaporins expression in the gastrointestinal tract of rat after mercury exposure

Impaired aquaporins expression in the gastrointestinal tract of rat after mercury exposure

Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model

Aquaporins in Infection and Inflammation

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