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dc.contributor.authorMukhopadhyay, Rita
dc.contributor.authorAgre, Peter
dc.contributor.authorRosen, Barry P.
dc.contributor.authorNielsen, Søren
dc.contributor.authorDiCarlo, Stephen E.
dc.contributor.authorLujan, Heidi L.
dc.contributor.authorLiu, Yangjian
dc.contributor.authorWang, Yiding
dc.contributor.authorRojek, Aleksandra
dc.contributor.authorYoshinaga, Masafumi
dc.contributor.authorZhou, Yao
dc.contributor.authorSong, Linhua
dc.contributor.authorCarbrey, Jennifer M.
dc.date.accessioned2010-04-27T13:57:57Z
dc.date.available2010-04-27T13:57:57Z
dc.date.issued2009-09-15
dc.identifier.citationProc Natl Acad Sci U S A. 2009 Sep 15;106(37):15956-60. Epub 2009 Sep 8. http://www.pnas.org/content/106/37/15956.fullen_US
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/34028
dc.description.abstractExpressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO(2), AQP9-null mice suffer reduced survival rates (LD(50), 12 mg/kg) compared with WT mice (LD(50), 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10-20 times more arsenic than WT mice. Within hours after NaAsO(2) injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only approximately 10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.en_US
dc.language.isoen_USen_US
dc.publisherNational Academy of Sciencesen_US
dc.subjectArsenic/toxicityen_US
dc.subjectArsenic/pharmacokineticsen_US
dc.subjectAquaporins/deficiencyen_US
dc.titleReduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null miceen_US
dc.typeArticleen_US


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